Novel l,7-dicarba-c/oso-dodecaborane(12) (meta-carbaborane)-derived carboxylic acids and amines suitable for peptide modification for application in boron neutron capture therapy (BNCT)

Technical Field

The present invention relates to Novel l,7-dicarba-c/oso-dodecaborane(12) (meta-carbaborane)- derived carboxylic acids and amines suitable for peptide modification for application in boron neutron capture therapy (BNCT).

Background

Since the discovery of dicarba-c/oso-dodecarboranes(12) (C2B10H12, carbaboranes, carboranes) in 1963, various applications [Boron Science, New Technologies and Applications, ed. N. S. Hosmane, ISBN 978-1-4398266-3-8, CRC Press: Boca Raton, FL, USA (2011).] have been found in catalysis [ (a) S. Bauer, S. Tschirschwitz, P. Lonnecke, R. Frank, B. Kirchener, M. L. Clarke, E. Hey- Flawkins, Eur. J. of Inorg. Chem. 2776 (2009); (b) S. Bauer, E. Hey-Hawkins, Phosphorus- Substituted Carbaboranes in Catalysis, in: Boron Science, New Technologies and Applications, chapter 22, ed. N. S. Hosmane, ISBN 978-1-4398266-3-8, CRC Press: Boca Raton, FL, USA, 513- 559 (2011); (c) S. E. Lyubimov, E. A. Rastorguev, T. A. Verbitskaya, E. A. Rastorguev, E. Hey- Hawkins, V. N. Kalinin, V. A. Davankov, Polyhedron 30, 1258 (2011); (d) S. E. Lyubimov, I. V. Kuchurov, A. A. Tyutyunov, P. V. Petrovskii, V. N. Kalinin, S. G. Zlotin, V. A. Davankov, E. Hey- Hawkins, Catalysis Commun. 11, 419 (2010); (e) S. E. Lyubimov, V. A. Davankov, K. N. Gavrilov, T. B. Grishina, E. A. Rastorguev, A. A. Tyutyunov, T. A. Verbitskaya, V. N. Kalinin, E. Hey-Hawkins, Tetrahedron Letters 51, 1682 (2010); (e) S. E. Lyubimov, V. A. Davankov, P. V. Petrovskii, E. Hey- Hawkins, A. A. Tyutyunov, E. G. Rys, V. N. Kalinin, J. Organomet. Chem. 693, 3689 (2008).], materials design [ (a) T. M. Keller, Carbon 40, 225 (2002); (b) A. Gonzalez-Campo, R. Ncinez, C. Vihas, B. Boury, New J. Chem. 30, 546 (2006); (c) F. Lerouge, C. Vihas, F. Teixidor, R. Ncinez, A. Abreu, E. Xochitiotzi, R. Santillan, N. Farfan, Dalton Trans. 1898 (2007).], and medicine [J. F. Valliant, K. J. Guenther, A. S. King, P. Morel, P. Schaffer, O. O. Sogbein, K. A. Stephenson, Coord. Chem. Rev. 232, 173 (2002).]. Dicarba-c/o50-dodecaboranes(12), in which two BH units of closo- Bi2Hi2 ^2_ are replaced by two CH vertices, have remarkable biological stability and two carbon atoms as well as specific boron atoms as starting point for various organic modifications.

Carbaboranes for medicinal applications are preferably used as boron carriers to design boron neutron capture therapy (BNCT) agents. The first BNCT agents were reported some time ago [M. F. Hawthorne, A. Maderna, Chem. Rev. 99, 3421 (1999).]. BNCT has been comprehensively summarised and the medicinal potential of carbaboranes has also been reviewed [M. F. Hawthorne, M. W. Lee, J. Neurooncol. 62, 33 (2003), V. I. Bregadze, I. B. Sivaev, S. A. Glazun, Anticancer Agents Med. Chem. 6, 75 (2006), I. B. Sivaev, V. I. Bregadze, Eur. J. Inorg. Chem. 1433 (2009), Z. J. Lesnikowski, Collect. Czech. Chem. Commun. 72, 1646 (2007).].

BNCT is based on the idea of selectively delivering boron compounds to tumour tissue, which is subsequently irradiated with non-hazardous, thermal neutrons. The latter cause a nuclear reaction with the ¹⁰ B isotope, which has a natural abundance of ca. 19.9% and a remarkable capability of capturing thermal neutrons with a capture cross section of ca. 3800 barn [M. F. Hawthorne, Angew. Chem. Int. Ed. 32, 950 (1993); Angew.Chem. 105, 997 (1993), A. H. Soloway, W. Tjarks, B. A. Barnum, F. G. Rong, R. F. Barth, I. M. Codogni, J. G. Wilson, Chem. Rev. 98, 1515 (1998).].

The ⁷ Li and ⁴ He nuclei released in the fragmentation of short-lived ¹¹ B*, which is formed upon thermal neutron capture of ¹⁰ B ( ¹⁰ B(n,a) ⁷ Li), are particles with a high linear energy transfer (high- LET). Thus, they may exert a highly destructive action on cells. Their travel distance is limited to a range of ca. 10 pm, which coincides with the diameter of most cells. Accordingly, there is a good chance to deposit a high radiation dose inside the cell without compromising the integrity of the surrounding tissue [M . F. Hawthorne, Angew. Chem. Int. Ed. 32, 950 (1993); Angew.Chem. 105, 997 (1993).].

Both the intracellular production of cytotoxic particles and their limited area of action are the major advantages of BNCT compared to classical chemotherapeutic methods [M. F. Hawthorne, Angew. Chem. Int. Ed. 32, 950 (1993); Angew.Chem. 105, 997 (1993).]. However, targeted delivery of ¹⁰ B into tumour cells and high and selective accumulation in tumour cells are important requirements for a BNCT agent [R. F. Barth, M. G. Vicente, O. K. Harling, W. S. Kiger, 3rd, K. J. Riley, P. J. Binns, F. M. Wagner, M. Suzuki, T. Aihara, I. Kato, S. Kawabata, Radiat. Oncol. 7, 146 (2012).]. For successful application of BNCT, a high rate of boron uptake is essential. It is assumed that a concentration of 30 pg ¹⁰ B per gram tumour (10 ⁹ boron atoms per cell) must be achieved to exert an effective dose in tumour cells [R. F. Barth, A. H. Soloway, J. Neurooncol. 33, 3 (1997).].

Up to now, only two boron-containing compounds have been investigated intensively in clinical trials: 4-dihydroxyborylphenylalanine (BPA) and the mercaptoundecahydrododecaborate (BSH) anion. Due to poor targeting (BSH) and low boron loading per molecule (BPA), comparably large quantities of these boron-delivery agents must be applied for reasonable tumour uptake [R. F. Barth, Appl. Radiat. Isotopes 67, S3 (2009).]. Therefore, compounds with a high affinity and selectivity to tumour cells represent an interesting option as boron carriers.

In the past two decades, mostly compact, boron-rich moieties, e.g., dodecahydrododecaborate(2-) (Bi Hi ^2_ ) and carbaboranes, have been functionalised and investigated as boron-delivering agents. The main problems to date are the availability of boron compounds which exhibit the necessary water solubility and low toxicity in high concentrations and the targeted delivery of ¹⁰ B into the tumour cells [M. F. Hawthorne, M. W. Lee, J. Neurooncol. 62, 33 (2003).].

We have, therefore, devised efficient syntheses for a wide variety of carbaborane derivatives which feature a carboxylic acid group for conjugation with tumour-selective peptides.

Carbaborane-Peptide Conjugates

Recently, peptides have captured much attention as therapeutic compounds [V. M. Ahrens, K. Bellmann-Sickert, A. G. Beck-Sickinger, Future Med. Chem. 4, 1567 (2012).]. Peptide compounds comprising boron moieties such as boronated starbust dendrimers or BSH, applicable for BNCT, have been described [ (a) J. Capala, R. F. Barth, M. Bendayan, M. Lauzon, D. M. Adams, A. H. Soloway, R. A. Fenstermaker, J. Carlsson, Bioconjug. Chem. 7, 7 (1996); (b) R. F. Barth, W. Yang, D. M. Adams, J. H. Rotaru, S. Shukla, M. Sekido, W. Tjarks, R. A. Fenstermaker, M. Ciesielski, M. M. Nawrocky, J. A. Coderre, Cancer Res. 62, 3159 (2002); (c) W. Mier, D. Gabel, U. Haberkorn, M. Eisenhut, Z. Anorg. Allg. Chem. 630, 1259 (2004).]. Also, carbaboranes have been integrated into the peptide sequences of well-known therapeutic peptides, especially for the selective delivery of a large amount of boron to tumour cells. Carbaborane-conjugated Tyr ³ -octreotate derivatives with high internalisation rates were developed to act as tumour-targeting vectors and exhibit mvi binding affinities to the somatostatin receptor subtype 2 depending on the spacer length between the carbaborane and the cyclic peptide [T. Betzel, T. Hess, B. Waser, J. C. Reubi, F. Roesch, Bioconjug. Chem. 19, 1796 (2008).]. These findings demonstrate the suitability of carbaborane-peptide conjugates as potential boron carriers for BNCT. Other peptides which are suggested as carrier systems for the targeted delivery of ¹⁰ B into the tumour cells are somatostatin (SST), epidermal growth factor (EGF), neurotensin, substance P, gastrin-releasing peptide (GRP), insulin-like growth factor (IGF), alpha-melanocyte stimulating hormone (a-MSH), cholecystokinin (CCK), vascoactive intestinal peptide (VIP), bombesin (BN), and neuropeptide Y (NPY) [I. U. Khan, A. G. Beck-Sickinger, Anticancer Agents Med. Chem. 8, 186 (2008).]. As a member of the pancreatic polypeptide family, NPY is composed of 36 amino acid residues and C- terminally amidated. It is one of the most abundant neuropeptides in the brain [K. Tatemoto, M. Ca r ¾9 A ¹ ) 'v J m ' Nature 296, 659 (1982).], binds to four Y-receptor s u lF y m^ ΐ! ⁸ /» ⁽ , ^8' ί 4¾ l d Y ₅ ) in nanomolar concentration and subsequently triggers receptor-mediated endocytosis [I. Bohme, J. Stichel, C. Walther, K. Mori, A. G. Beck-Sickinger, Cell. Signal.20, 1740 (2008).]. The signal transduction of Y-receptors follows a G protein-coupled (GPC) receptor cascade [M. C. Michel, A. G. Beck-Sickinger, H. Cox, H. N. Doods, H. Herzog, D. Larhammar, R. Quirion, T. Schwartz, T. Westfall, Pharmacol. Rev.50, 143 (1998)., P. M. Rose, P. Fernandes, J. S. Lynch, S. T. Frazier, S. M. Fisher, K. Kodukula, B. Kienzle, R. Seethala, J. Biol. Chem.270, 22661 (1995) and erratum p. 29038.]. Beck-Sickinger et al. have developed a modified neuropeptide Y, [F ⁷ , P ³⁴ ]-NPY, that was shown to preferentially bind to the human Yi-receptor compared to other Y-receptor subtypes with a high tolerance towards modifications [R. M. Soil, M. C. Dinger, I. Lundell, D. Larhammer, A. G. Beck-Sickinger, Eur. J. Biochem.268, 2828 (2001).]. Conjugates of o/tfto-carbaborane derivatives with [F ⁷ , P ³⁴ ]-NPY as a potent selective carrier for ¹⁰ B into breast tumour cells have already been prepared; binding studies and intracellular inositol phosphate (IP) accumulation assays confirmed nanomolar affinity and activity of the modified analogues despite the large carbaborane cluster. Internalisation studies using fluorescence-tagged Y-receptors revealed excellent and receptor subtype specific uptake of the conjugates into respective cells [V. M . Ahrens, R. Frank, S. Stadlbauer, A. G. Beck-Sickinger, E. Hey-Hawkins, J. Med. Chem.54, 2368 (2011), V. M . Ahrens, R. Frank, S. Boehnke, C. L. Schiltz, G. Hampel, D. S. Iffland, N. H. Bings, E. Hey-Hawkins, A. G. Beck-Sickinger, ChemMedChem 10, 164 (2015).]. The disadvantage of ortho- carbaborane derivatives is their low stability under basic conditions. O/tfto-carbaborane undergoes a deboronation in the presence Lewis bases such as amines, fluorides, alkoxides or thiolates. Under these conditions one boron atom of the cluster is removed leading to a charged nido-c arbaborane(l-) species [M. Scholz, E. Hey-Hawkins, Chem. Rev. Ill, 7035 (2011).]. This problem can be solved by using meta-carbaborane that is highly stable under basic conditions.

Since the hydrogen atoms of boron clusters have a strong hydridic character, carbaboranes are extremely hydrophobic and, therefore, poorly soluble in water; this can lead to aggregation of the clusters in aqueous media. This problem can be overcome by attaching hydrophilic groups to the carbaborane cage such as sugar derivatives that strongly increase the solubility of carbaboranes in water [(a) S. Stadlbauer, P. Lonnecke, P. Welzel, E. Hey-Hawkins, Europ. J. Org. Chem.2009, 6301-6310; (b) S. Stadlbauer, P. Lonnecke, P. Welzel, E. Hey-Hawkins, Europ. J. Org. Chem.2010, 3129-3139; (c) E. Hey-Hawkins, S. Stadlbauer, Neue chemische Verbindung und deren Verwendung in der Medizin, insbesondere fur die Verwendung in der Tumortherapie, PCT/EP2008/060649.]. _n-t WO 2019/115617 Invention PCT/EP2018/084568

The compounds according to the invention of general formula (I) can be prepared according to the following scheme 1. The scheme and procedures described below illustrate synthetic routes to the compounds of general formula (I) of the invention and are not intended to be limiting. It is clear to the person skilled in the art that the order of transformations as exemplified in the scheme can be modified in various ways. The order of transformations exemplified in this scheme is therefore not intended to be limiting. In addition, interconversion of any of the substituents can be achieved before and/or after the exemplified transformations. These modifications can be such as the introduction of protecting groups, cleavage of protecting groups, reduction or oxidation of functional groups, halogenation, metalation, substitution or other reactions known to the person skilled in the art. These transformations include those which introduce a functionality which allows for further interconversion of substituents. Appropriate protecting groups and their introduction and cleavage are well-known to the person skilled in the art (see for example T.W. Greene and P.G.M. Wuts in Protective Groups in Organic Synthesis, 3 ^rd edition, Wiley 1999). Specific examples are described in the subsequent paragraphs.

A route for the preparation of compounds of general formula (I) are described in the following schemes.

The general reactions of scheme 1 were carried out under inert atmosphere using the Schlenk technique and dry nitrogen gas as an inert gas. Commercial reagents were used as purchased. Solid starting materials were placed in the reaction flasks, evacuated and purged with nitrogen three times, respectively, and then dissolved in the appropriate dry solvent. The detailed reaction conditions were given in the corresponding procedure. All compounds were purified using column chromatography and characterized at least with nuclear magnetic resonance spectroscopy and mass spectrometry.

Compounds (14) and (4) can be prepared according to procedures available from the public domain, as understandable to the person skilled in the art. Specific examples are described in the Experimental Section.

[scheme 1]

As shown in scheme 1 the starting compounds 9-(Mercapto)-l,7-dicarba-c/oso- dodecaborane(12) and l,2:3,4-Di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6-t riflate were synthesized according to the given literature: [L. I. Zakharkin, I. V. Pisareva, Phosphorus and Sulfur and Rel. Elem. 20, 357 (1984).] and [M. Brackhagen, H. Boye, C. Vogel, J. Carbohydrate Chem. 20, 31 (2001).]. 9-(Mercapto)-l,7-dicarba-c/oso-dodecaborane(12) was synthesized by adding aluminiumchloride and disulfur dichloride to a solution of 1,7-dicarba -closo- dicarbaborane(12) in dichloromethane. The following mixture was stirred for four hours at 40°C. The resulting intermediate was reduced with nascent hydrogen formed by the reaction of excess zinc powder in a one to one mixture of glacial acetic acid and hydrochloric acid at refluxing temperatures. 9-(Mercapto)-l,7-dicarba-c/oso-dodecaborane(12) was purified by extraction with 11% aqueous potassium hydroxide solution from diethyl ether and precipitation with concentrated hydrochloric acid. l,2:3,4-Di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6- triflate was synthesized by adding pyridine and trifluoromethane sulfonic acid anhydride to a solution of l,2:3,4-Di-0-isopropylidene-a-D-galactopyranose in dichloromethane at 0°C. The raw product, which was obtained after three hours of stirring at room temperature, was washed with water, 17% potassium hydrogen sulfate solution, saturated sodium hydrogen carbonate solution, extracted with chloroform and purified by column chromatography with a three to one eluent mixture of n-hexane and ethyl acetate. 2-Chloro-4,6-bis(l,7-dicarba-c/oso-dodecaboran-9- ylthio)-l,3,5-triazine was synthesized by reacting cyanuric chloride and 9-(Mercapto)-l,7- dicarba-c/oso-dodecaborane(12) under presence of diisopropylethylamine in acetonitrile at refluxing temperature for five hours. After removal of the solvent under reduced pressure the raw product was extracted with ethyl acetate and diethyl ether from water. The product was proved to be pure enough for further reactions by thin layer chromatography with a one to two mixture of ethyl acetate and n-hexane. The following substitution reaction using mercaptoacetic acid as a nucleophile was performed in acetonitrile under presence of diisopropylethylamine and reflux conditions for three hours. While using glycine and /V _c r(ferf-butoxycarbonyl)-L-lysine as a nucleophile the addition of water was necessary and the usage of sodium hydroxide as a base instead of diisopropylethylamine. In these cases the reactions were heated to refluxed for one day, in the case of glycine, and 18 hours, in the case of lysine. All three derivatives were purified using column chromatography and either mixtures of ethyl acetate and n-hexane or mixtures of acetone and n-hexane. Sometimes it was necessary to add 2.5% of glacial acetic acid to the eluent mixture. The last reaction, concerning the glycine derivative, which was aimed to introduce the galactopyranosyl moiety at the secondary amine, was carried out in tetrahydrofuran with presence of potassium carbonate as a base. The reaction was stirred for two days at ambient temperature and stopped by adding distilled water. After extraction of the aqueous phase with diethyl ether and purification via column chromatography with a three to one mixture of n- hexane and ethyl acetate the ester (l',2':3',4'-Di-0-isopropylidene-6'-deoxy-a-D-galactopyranos - 6'-yl)[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5 -triazin-2-yl]glycinate was obtained, not the desired compound /V-[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tr iazin-2- yl]-/V-(l',2':3',4'-di-0-isopropylidene-6'-deoxy-a-D-galacto pyranos-6'-yl)glycine. The reason for this kind of reaction and the following observation is caused by the low nucleophilicity of the secondary amine group which is directly attached to the triazine ring. This situation facilitates the delocalization of the free electron pair of the amine group in the triazine ring and reduces its nucleophilic character. Furthermore, it is known that carboxylic acids could react with triflates under basic conditions to form esters like it happened here. [G. Hughes, P. O'Shea, J. Goll, D. Gauvreau, J. Steele, Tetrahedron, 2009, 65, 3189-3196.] In our case it means that l,2:3,4-Di-0- isopropylidene-6-deoxy-a-D-galactopyranosyl-6-triflate reacted with the free carboxylic acid of the glycine derivative [4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-triaz in-2-yl]glycine. Because of this observation a new synthetic strategy was developed where the galactopyranosyl moiety was introduced first before the glycine moiety was attached to the triazine ring. This pathway is shown below in scheme 2.

[scheme 2]

In scheme 2 9-(Mercapto)-l,7-dicarba-c/oso-dodecaborane(12) and l,2:3,4-Di-0-isopropylidene- 6-deoxy-a-D-galactopyranosyl-6-triflate were synthesized according to literature like before in scheme 1. The first reaction uses fe/t-butyl glycinate as a glycine derivative to prevent reactions with l,2:3,4-Di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6-t riflate and the free carboxylic acid. In this case the substitution occurs at the primary amine group of the glycine derivative. This reaction was performed in acetonitrile with presence of diisopropylamine. After two days of stirring at 45°C the reaction was continued in an one-pot manner a nd cyanuric chloride and an additional portion of diisopropylethylamine were added at 0°C. The mixture was stirred at 35°C for two more days and stopped afterwards by addition of a saturated aqueous sodium chloride solution. After extraction of the aqueous phase with ethyl acetate and purification via column chromatography the desired tertiary amine was obtained. fert-Butyl-/V-[4,6-bis(l,7-dicarba- c/oso-dodecaboran-9-ylthio)-l,3,5-triazin-2-yl]-A/-(l',2':3' ,4'-di-0-isopropylidene-6'-deoxy-a-D- galactopyranos-6'-yl)glycinate was synthesized from the dichloride tert-Butyl-/V-(4,6-dichloro- l,3,5-triazin-2-yl)-/V-(l',2':3',4'-di-0-isopropylidene-6'-d eoxy-a-D-galactopyranos-6'-yl)glycinate and 9-(mercapto)-l,7-dicarba-c/oso-dodecaborane(12) in acetonitrile with potassium carbonate as a base. The reaction mixture was stirred under reflux conditions for three days. The reaction was stopped by adding a saturated aqueous sodium chloride solution. After extraction of the aqueous phase with ethyl acetate and purification with column chromatography, using a mixture of ethyl acetate and n-hexane as the eluent, the product was obtained as a white solid. The last reaction step, concerning the deprotection of the te/T-butyl ester without the cleavage of the isopropylidene protecting groups of the galactopyranosyl moiety, was carried out in dry toluene with 3 A molecular sieves as a drying agent. Trifluoroacetic acid was used as the proton source for the cleaveage of the ester. I n this reaction we utilized the fact, that the deprotection of acetonide protecting groups require the presence of water to be cleaved and the cleavage of terf-butyl esters don't. The reaction mixture was stirred and heated to 80°C for three days. The reaction was stopped by adding a saturated aqueous sodium bicarbonate solution. The molecular sieves were filtered off and the aqueous phase was extracted with ethyl acetate. After column chromatography with pure ethyl acetate the free acid was obtained. It was checked by nuclear magnetic resonance spectroscopy if the isopropylidene protecting groups of the galactopyranosyl moiety are still intact or not.

When using fert-Butyl A/-(2-aminoethyl)carbamate as a starting material to produce the amine derivative containing the galactopyranosyl moiety the general synthetic strategy was used like described above. Only in the last step, when the terf-butyloxycarbonyl protecting group should be cleaved, dry dichloromethane and 50 equivalents of trifluoroacetic acid were used and the reaction was carried out at room temperature for four hours.

Com pounds according to this invention have a unique profile as the provide - despite the very high number of boron atoms per molecule - a high solubility in water and a high metabolic stability. These compounds can easily be coupled to tumor-selective peptides thereby selectively targeting certain tumor cells and making an injection of these compounds into the tumor redundant. By using ¹⁰ B-enriched starting materials effectiveness can even be increased.

I n case the carbaboran compound described herein has a free ca rboxyl group, it is treated in a suitable solvent with diisopropylcarbodiimide (DIC) and 1-hydroxybenzotriazole (HOBt). It is thus converted into an active ester. Subsequently, the active ester readily reacts with the free amino group of tumor-selective peptides side chain (especially the free, unprotected amino group on the e-carbon of lysine), forming the amide bond.

I n case the carbaborane compound has a free amino group, the tumor-selective peptide - having all carboxyl groups which are not to be modified protected appropriately - is treated in a suitable solvent with DIC and HOBt so that the free carboxyl groups on the peptide side chains are corn cu ^iiiu^fZcive esters. Subsequently, the peptide reacts with the carbaboran compound to the corresponding conjugates that are linked by amide bond (W. Konig, R. Geiger, Chem. Ber. 1970, 103, 788-798).

Ortho-c arboranes are known to be metabolically instable that impairs their use for medical purposes. [E. Svantesson, J. Pettersson, A. Olin, K. Markides, S. Sjoberg, Acta Chem. Scand. 1999, 53, 731-736.]. However, metabolisation studies of compounds containing meta-carboranes according to this invention showed a reduced metabolisation after 24 h in blood plasma (5 - 10 % disintegration of meta-carboranes compared to 27 % disintegration of ortho-carboranes).

Further, by virtue of the symmetry properties of the carbaborane core, its positions 1 and 7 in 9- monosubstituted carbaborane intermediates are not topologically identical, i.e. not interchangable by rotation as shown in the Scheme le below. This also applies to instances where reference is made to such substitution at a position corresponding to position 1.

1-Gal, 9-thio 7-Gal, 9-thio

Scheme le: Topological features of carbaborane core positions 1 and 7

Therefore, regioisomeric mixtures may result when substituents, such as those derived from the monosaccharide intermediates disclosed herein, are attached to said position 1 or 7, as the case may be. Hence, the display of a carbaborane substituted at one of said positions 1 and 7, as exemplarily shown in Scheme If, below, and also in the claims and the specification herein refers to a respective compound featuring said substitution at position 1 (but not at position 7), or a respective compound featuring said substitution at position 7 (but not at position 1), or a regioisomeric mixture thereof. This also applies to instances where reference is made to such substitution at position 1. Accordingly, and as far as compounds with one monosaccharide based substituent attached to position 1 or 7 are concerned, the present invention covers compounds of formula (I) featuring said monosubstitution at position 1, compounds featuring said monosubstitution at position 7, and regioisomeric mixtures thereof.

Sac

Scheme If: Carbaborane moiety encoding for substitution at position 1, position 7, or a regioisomeric mixture reflecting both monosubstitutions.

It is possible for the compounds of general formula (I) to exist as isotopic variants. The invention therefore includes one or more isotopic variant(s) of the compounds of general formula (I), particularly compounds of general formula (I) enriched in the boron isotope ¹⁰ B.

The term "Isotopic variant" of a compound or a reagent is defined as a compound exhibiting an unnatural proportion of one or more of the isotopes that constitute such a compound.

The term "Isotopic variant of the compound of general formula (I)" is defined as a compound of general formula (I) exhibiting an unnatural proportion of one or more of the isotopes that constitute such a compound.

The expression "unnatural proportion" means a proportion of such isotope which is higher than its natural abundance. The natural abundances of isotopes to be applied in this context are described in "Isotopic Compositions of the Elements 1997", Pure Appl. Chem., 70(1), 217-235, 1998.

Examples of such isotopes include stable and radioactive isotopes of hydrogen, boron, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as ² H (deuterium), ³ H (tritium), ¹⁰ B, ⁿ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁷ 0, ¹⁸ 0, ³² P, ³³ P, ³³ S, ³⁴ S, ³⁵ S, ³⁶ S, ¹⁸ F, ³⁶ CI, ⁸² Br, ¹²³ l, ¹²⁴ l, ¹²⁵ l, ¹²⁹ l and ¹³¹ l, respectively.

With respect to the treatment and/or prophylaxis of the disorders specified herein the isotopic variant(s) of the compounds of general formula (I) preferably contain ¹⁰ B (" ¹⁰ B-containing compounds of general formula (I)"). The ¹⁰ B boron isotope features an effective nuclear cross section of 3835(9) barn (cf. ¹ H features 0.3326(7) barn, ⁿ B 0.0055(33) barn, ¹² C 0.00353(7) barn, see e.g. Sears, Valery F., Neutron News, 1992, 3, 26-37). Upon reaction with neutrons of low kinetic energy (thermal or epithermal neutrons), alpha particles ( ⁴ He ²⁺ nuclei) and lithium-7 nuclei are formed. These high linear energy transfer (LET) particles convey their lethal destructive effects only to boron-containing cells, as discussed in the background section in more detail. Since only the ¹⁰ B isotope, but not the ⁿ B isotope undergoes neutron capture, ¹⁰ B-enriched agents are preferred isotopic variants of the compounds of the general formula (I). Other isotopic variants of the compounds of general formula (I) in which one or more radioactive isotopes, such as ³ H or ¹⁴ C, are incorporated are useful e.g. in drug and/or substrate tissue distribution studies. These isotopes are particularly preferred for the ease of their incorporation and detectability. Positron emitting isotopes such as ¹⁸ F or ⁿ C may be incorporated into a compound of general formula (I). These isotopic variants of the compounds of general formula (I) are useful for in vivo imaging applications. Deuterium-containing and ¹³ C-containing compounds of general formula (I) can be used in mass spectrometry analyses in the context of preclinical or clinical studies. Replacement of hydrogen by deuterium may also alter the physicochemical properties (such as for example acidity, basicity, lipophilicity and/or the metabolic profile of the molecule and may result in changes in the ratio of parent compound to metabolites or in the amounts of metabolites formed. Such changes may result in certain therapeutic advantages and hence may be preferred in some circumstances.

Isotopic variants of the compounds of general formula (I) can generally be prepared by methods known to a person skilled in the art, e.g. by employing ¹⁰ B-enriched boric acid ¹⁰ B(OH)3 as starting material for the preparation of carbaborane synthons used for the preparation of compounds of the general formula (I), according to the schemes and/or examples herein. ¹⁰ B-enriched boric acid has become commercially available from a plethora of suppliers (e.g. Katchem spol. S r. o., Elisky Krasnohorske 123/6, 110 00 Josefov, Czech Republic; Boron Specialties LLC, Laboratory & Warehouse, 2301 Duss Avenue, Ste. 35, Ambridge, PA 15003 USA), in isotopic purities up to 99+%, and can be elaborated into ¹⁰ B-enriched carbaborane synthons by multiple methods known to the person skilled in the art (see e.g. Yinghuai, Z., Widjaja, E., Lo Pei Sia, S., Zhan, W., enter, K., Maguire, J. A., Hosmane, N. S., Hawthorne, M.F., J. Am. Chem. Soc., 2007, 129, 6507- 6512; Adams, L., Tomlinson, S., Wang, J., Hosmane, S. N., Maguire, J. A., Hosmane, N. S., Inorg. Chem. Commun., 2002, 5, 765-767.; Scholz, M., Hey-Hawkins, E., Chem. Rev., 2011, 111, 7035- 7062; Grimes, Russel N.: Carboranes. Third Edition, Academic Press (Elsevier), 2016, ISBN: 9780128018941) Furthermore, carbaborane synthons with high isotopic enrichment of ¹⁰ B up to 99+% are also commercially available from Katchem spol. s r. o., Czech Republic (http//:www. katchem.cz/en).

Deuterium can be introduced in place of hydrogen in the course of the synthesis of compounds of the general formula (I) by many methods well known to the person skilled in the art, e.g. deuterium from D ₂ 0 can be incorporated into said compounds directly or indirectly, or by catalytic deuteration of olefinic or acetylenic bonds using deuterium gas. The terms " ¹⁰ B-containing compound of general formula (I)", " ¹⁰ B-containing compound of general formula (la)", or " ¹⁰ B-containing compound of general formula (lb)", as the case may be, are defined as a compound of general formulae (I), (la), or (l b), respectively, in which one or more boron atom(s) in its/their natural isotopic composition is/are replaced by one or more ¹⁰ B atom(s) and in which the abundance of ¹⁰ B at each respective position of the compound of general formula (I) is higher than the natural abundance of ¹⁰ B, which is about 20%. Particularly, in a ¹⁰ B -containing compound of general formula (I), (la) or (lb), the abundance of ¹⁰ B of each boron atom of the compound of general formula (I), (la) or (lb) is higher than 30%, 40%, 50%, 60%, 70% or 80%, preferably higher than 90%, 95%, 96% or 97%, even more preferably higher than 98% or 99%. It is understood that the abundance of ¹⁰ B of each boron atom can be either identical with, or independent of the abundance of ¹⁰ B at other boron atom(s).

I n another embodiment the present invention covers a ¹⁰ B-containing compound of general formula (I), in which the abundance of ¹⁰ B of each boron atom of the compound of general formula (I) is higher than 90%,

A monosaccharide is a carbohydrate of the formula C _n (H ₂ 0) _n , that cannot be hydrolyzed to simpler sugars, such as glucose, galactose, fructose or ribose. There are natural and synthetic monosaccharides. Especia lly the following monosaccharides can be coupled to carbaboranes of this invention.

PG ¹ , PG ² , PG ³ , PG ⁴ represent protecting groups suitable for the protection of hydroxy groups on saccharides, such as benzyl or acetyl, and in which preferably two groups selected from PG ¹ , PG ² , PG ³ , PG ⁴ attached to hydroxy groups on adjacent carbon atoms together form the group - C(CH ₃ ) ₂ -.

One aspect of this invention is related to compounds of general formula I

(l}1 in which

XI is -N(H)-, -N(G)- or -S-,

X2 is -CH ₂ -COOH, -CH2-COOG, -(CH ₂ )4-C(COOH)-NH-COO- ^tert Butyl or -(CH ₂ ) ₂ -NH ₂

CB is· wherein

wherein

^* marks the position where CB* is coupled to compound of formula (I)

X and Y are independently of each other -H and -G and

G is natural or synthetic monosaccharide in which the hydroxygroups are protected

as well as the related ¹⁰ B-enriched compounds,

and its pharmaceutically acceptable salts, solvates and hydrates and mixtures thereof. Another aspect is related to compound in which G is one of the following monosaccharides:

and in which

R is a protective group,

R' is -H,

as well as the related ¹⁰ B-enriched compounds,

and its pharmaceutically acceptable salts, solvates and hydrates and mixtures thereof.

A further aspect is related to compounds in which the protective group R is acetate or isopropylidene as well as the related ¹⁰ B-enriched compounds, and its pharmaceutically acceptable salts, solvates and hydrates and mixtures thereof.

A fourth aspect is related to compounds in which G is a-D-Gal Gal well as the related ¹⁰ B-enriched compounds, and its pharmaceutically acceptable salts, solvates and hydrates and mixtures thereof. The invention is also related to compounds:

2-{[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tr iazin-2-yl]thio},

[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-triaz in-2-yl]glycine,

L/ ⁶ -[4, 6-Bis(l, 7-dicarba-c/oso-dodeca boran-9-ylthio)-l, 3, 5-triazi n-2-yl]-/V ² -( tert- butoxycarbonyl)-L-lysine,

as well as the related ¹⁰ B-enriched compounds, and its pharmaceutically acceptable salts, solvates and hydrates and mixtures thereof.

Another aspect of this invention is related to compounds of formula (I) with the provisio, that at least one of XI, X2, X or Y contains or is -G as well as the related ¹⁰ B-enriched compounds, and its pharmaceutically acceptable salts, solvates and hydrates and mixtures thereof.

Another further aspect of this invention is related to

/V-[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tr iazin-2-yl]-/\/-( ,2 ^, :3',4 ^, -di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)glycine and

N ¹ -(4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3, 5-triazin-2-yl)-N ¹ -(((l',2':3',4'-di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)ethane-l, 2-diamine.

A further aspect of this invention is related to the use of compounds for the preparation of carbaborane peptide conjugates.

Experimental Section

Materials and methods

Disulfur dichloride, trimethyl borate, peracetic acid (32% in acetic acid), paraformaldehyde, pyridine, iodine, ethyl formate, trifluoromethanesulfonic anhydride, carbon dioxide, iodoacetic acid, diisopropylethyl amine, sodium hydride (60% in mineral oil), bromoacetic acid, trifluoroacetic acid, mercury(ll) acetate, 2-mercapto ethanol, copper(l) iodide, bis(tri phenyl phosphane)palladium(ll) dichloride, l,2:3,4-di-0-isopropylidene-a-D- galactopyranose, cyanuric chloride, 2,4,6-collidine, thioglycolic acid, glycine, tert-butyl glycinate hydrochloride, /V _a -(fert-butoxycarbonyl)-L-lysine, and /V-(tert-butoxycarbonyl)-L-serine methyl ester were commercially available; n-BuLi was provided by Rockwood Lithium GmbH; ortho-, meta-, para- carbaborane, l-bromomethyl-o/t/?o-carbaborane and the boron-10 enriched meta- carbaborane were obtained from Katchem (Czech Republic). Hydrogen disulfide was prepared in a reaction of iron(ll) sulphide with concentrated hydrochloric acid. Deuterated solvents for NMR spectroscopy were purchased from euriso-top ^® . Lithiation reactions were carried out under nitrogen by using Schlenk techniques. Anhydrous diethyl ether, dichloromethane and tetrahydrofuran were obtained with an MBRAUN solvent purification system MB SPS-800. Acetonitrile was dried over CaH, distilled and stored over molecular sieve (3 A) under nitrogen atmosphere. Methanol was dried over magnesium methoxide, distilled and stored over molecular sieve (3 A) under nitrogen atmosphere. Acetic acid was dried over acetic anhydride and potassium permanganate, distilled and stored over molecular sieve (3 A) under nitrogen atmosphere. All other solvents were purchased and used as received. Thin-layer chromatography (TLC) with silica gel 60 F254 on glass available from Merck KGaA was used for monitoring the reactions. Carbaborane-containing spots were visualised with a 1-10% solution of PdCh in methanol. For chromatography, silica gel (60 A) with a particle diameter in the range of 0.035 to 0.070 mm, the Biotage ^® Isolera 1 automatic purification system or the Biotage ^® Isolera 4 automatic purification system with SNAP (particle diameter: 0.040 to 0.065 mm) and SNAP Ultra (spherical particle, diameter: 0.025 mm) cartridges was used. The carbaborane species were detected by an integrated UV/Vis detector (Isolera 1) or evaporative light scattering detector (ELSD) A-120 (Isolera 4) of the Biotage ^® company. For chromatography, solvents were distilled before use. NMR spectra

NM R measurements were carried out on a Bruker AVANCE II I HD spectrometer with an Ascend™ 400 magnet. Tetramethylsilane was used as internal standard, and ⁿ B-NMR spectra were referenced to the X scale [R. K. Harris, E. D. Becker, S. M . Cabral de Menezes, R. Goodfellow, P. Granger, N MR nomenclature. Nuclear spin properties and conventions for chemical shifts (I UPAC Recommendations 2001). Pure App!. Chem. 73, 1795 (2001).]. All chemical shifts are reported in ppm. Assignment of the ¹ H and ¹³ C signals was based on 2D NM R spectra (H,H-COSY, HMQC, HSQC, HM BC). Identification of the boron atom attached to sulfur was possible by comparison of the proton-coupled and -decoupled“B-NMR spectra.

On the following pages, some NM R signals that appear as broad overlapping signals with the shape of a multiplet in either ¹ H-, ¹¹ B{ ¹ H}-, ¹¹ B-, ¹⁰ B{ ¹ H}- or ¹⁰ B-NM R spectra are just described as 'br' (broad). In this case, the superscript a is added (br ^a ).

Infrared spectra

IR data were obtained with a Perkin-Elmer FT-IR spectrometer Spectrum 2000 on KBr pellets and on a Thermo Scientific Nicolet iS5 with an ATR unit in the range from 4000 to 400 cm ¹ . All detected signals were interpreted as w, m or s, which means weak, medium or strong, respectively.

Examples

Ex 4: 9-(Mercapto)-l,7-dicarba-c/oso-dodecaborane(12) (4)

(CAS 64493-44-3)

o = B atom

• = BH group

The compound was prepared according to the literature [L. I. Zakharkin, I. V. Pisareva, Phosphorus and Sulfur and Rel. Elem. 20, 357 (1984).].

9-(Mercapto)-l,7-dicarba-c/oso-dodecaborane(12) shows high solubility in common organic solvents. It crystallizes very well from diethyl ether, chloroform or dichloromethane. The neutral compound isn't soluble in water, but the anionic thiolate is very soluble in water under basic conditions.

Yield: 8.64 g (49.0 mmol, 71%)

^! H-NMR (400 MHz, CDCIB): d = 0.47 (m, 1H, SH), 1.44 - 3.41 (br ^a , m, 9H, B10H9), 2.98 (br s, 2H, CH) ppm.

“B^HJ-NMR (128 MHz, CDCI ₃ ): d = -2.6 (s, IB), -5.8 (s, 2B), -8.9 (s, IB), -12.5 (s, 2B), -13.8 (s, 2B), -17.6 (s, IB), -20.8 (s, IB) ppm.

Ex 13: 9-(ferf-Butylthio)-l,7-dicarba-c/oso-dodecaborane(12)

The following procedure is performed according to the synthesis for the o/tfto-carbaborane derivative [R. Frank, S. Boehnke, A. Aliev, E. Hey-Hawkins, Polyhedron 39, 9 (2012).].

3.00 g (17.02 mmol, 1.0 eq.) 9-(mercapto)-l,7-dicarba-c/oso-dodecaborane(12) (Ex 4) is suspended in 140 ml tBuOH/TFA = 1/6 (v/v) and DCM is added dropwise until the mixture turns into a clear solution. The solution is kept at ambient temperature without stirring for 8 days during which a red-brown solution is formed. The solution is quenched with Na ₂ C03 at 0 °C. Afterwards, the solution is diluted with 600 ml distilled water and NaOH is added until pH = 12 is reached. The aqueous phase is extracted three times with 300 ml DCM. The combined organic phases are dried over Na ₂ S0 ₄ , filtered and then the solvent is evaporated under reduced pressure giving 4.50 g of a yellow-brown oil, which crystallizes over time. The raw product is purified by several recrystallization steps in methanol yielding 2.93 g (12.55 mmol, 74% yield) pale yellow crystals.

¹ H-NMR (400 MHz, CDCI ₃ ): d = 1.45 (s, 9H, C(C ³ H ₃ ) ₃ ), 1.7 - 3.5 (br ^a , 9H, BioHg), 2.95 (br, s, 2H, 2xC ¹ H) ppm.

¹¹ B{ ¹ H}-NMR (128 MHz, CDCI ₃ ): d = -1.0 (br, IB, BS), -6.3 (br, 2B), -9.6 (br, IB), -13.0 (br, 2B), - 14.0 (br, 2B), -17.7 (br, IB), -20.1 (br, IB) ppm.

B-NMR (128 MHz, CDCI ₃ ): d = -1.0 (br, s, IB, BS), -6.3 (d, I/BH = 165 Hz, 2B), -9.6 (d, I/BH = 153 Hz, IB), -13.4 (m, 4B), -17.7 (d, I/BH = 182 Hz, IB), -20.1 (d, I/BH = 182 Hz, IB) ppm.

13 C{ ¹ H}-NMR (100 MHz, CDCI ₃ ): d = 32.7 (s, C(C ³ H ₃ ) ₃ ), 44.4 (s, C _q ² ), 53.9 (s, 2c^H) ppm

Elemental analysis:

Calculated for CeH ₂ oBioS: C = 31.01% H = 8.68%;

found: C = 32.15% H = 8.41% Ex 14: l,2:3,4-Di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6-t riflate (14)

(CAS 71001-09-7)

The compound is prepared according to the literature [M. Brackhagen, H. Boye, C. Vogel, J. Carbohydrate Chem. 20, 31 (2001).].

The reaction is performed under nitrogen.

7.50 g (28.80 mmol, 1.0 eq.) l,2:3,4-di-0-isopropylidene-a-D-galactopyranose are mixed with 7.6 ml (6.98 g, 57.60 mmol, 2.0 eq.) dry 2,4,6-collidine. The mixture is dissolved in 300 ml dry DCM. 7.7 ml (13.00 g, 46.08 mmol, 1.6 eq.) trifluoromethanesulfonic anhydride are added dropwise over 30 minutes at ambient temperature to this solution. The reaction mixture turns deep yellow during the addition. Over a stirring period of 4 hours at ambient temperature, the mixture turns orange. The reaction is quenched by pouring it onto 300 ml of iced water. The phases are separated and the water phase is extracted two times with 100 ml chloroform. The combined organic phases are washed two times with 250 ml of an aqueous 17% KHSO ₄ solution. The organic phase is washed two times with 200 ml of iced water, two times with 250 ml of a saturated NaHC0 ₃ solution, once with 300 ml iced water and finally once with 300 ml of a saturated NaCI solution. The organic phase is dried over Na ₂ S0 ₄ . The solution is concentrated by reduced pressure. TLC shows the product at an R _f -value of R _f = 0.46 (n-hexane/ethyl acetate = 3/1 v/v). The crude product is purified by column chromatography over silica using an isocratic n-hexane/ethyl acetate = 3/lmixture (v/v) as eluent, yielding 10.54 g (26.80 mmol, 93%) of a yellow oil, which slowly solidifies in the fridge.

l,2:3,4-Di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl- 6-triflate is a yellow, thick oil which is stable under dry nitrogen. It degrades slowly in moist air. It is stored under dry nitrogen at minus twenty degrees. It reacts readily with nucleophiles like thiolates, amines, alcoholates.

^! H-NM R (400 MHz, CDCI3) : d = 1.34 (s, 3H, CH ₃ ), 1.34 (s, 3H, CH ₃ ), 1.45 (s, 3H, CH ₃ ), 1.53 (s, 3H, CH ₃ ), 4.12 (ddd, ³ 7 _H H = 7.0 HZ, ³ J _H H = 4.7 HZ, ³ 7 _H H = 2.0 HZ, lH, CH ⁵ ), 4.25 (dd, J _H H = 7.8 Hz, I/HH = 2.0 Hz, 1H, CH ⁴ ), 4.36 (dd, ³ 7 _H H = 5.0 HZ, 7HH = 2.6 Hz, 1H, CH ² ), 4.55 - 4.68 (m, 3H, CH ³ , CH ⁶ ₂ ), 5.54 (d, ³ _H H = 4.9 Hz, 1H, CH ¹ ) ppm.

¹³ C{ ¹ H}-NMR (100 MHz, CDCI ₃ ): d = 24.4 (s, C ⁹ ' H ₃ ), 24.8 (s, C ⁹ ' H ₃ ), 25.8 (s, C ⁹ ' H ₃ ), 25.9 (s, C ^9,11 H ₃ ), 66.1 (s, C ⁵ H), 70.2 (s, C ² H), 70.4 (s, C ⁴ H), 70.6 (s, C ³ H), 74.6 (s, C ⁶ H ₂ ), 96.1 (s, ^H), 109.1 (s, C ⁸ ' ¹⁰ (CH ₃ ) ₂ ), 110.1 (s, C ⁸ ' ¹⁰ (CH ₃ ) ₂ ), 118.6 (q, ^CF = 320 Hz, C ⁷ F ₃ ) ppm.

Ex 17: l-( ,2':3' _f 4'-0-disopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl )-9-(ferf-butylthio)-l,7- dicarba-c/oso-dodecaborane(12)

The following procedure is performed according to the synthesis for the o/tfto-carbaborane derivative [see R. Frank, S. Boehmke, A. Aliev, E. Hey-Hawkins, Polyhedron 39, 9 (2012)].

2.97 g (12.78 mmol, 1.0 eq.) 9-(te/t-butylthio)-l,7-dicarba-c/oso-dodecaborane(12) (Ex 13) is dissolved in 100 ml diethyl ether and cooled to 0 °C and 8.72 ml (1.45 M in n-hexane, 12.64 mmol, 0.9 eq.) n-butyllithium is added dropwise. The reaction is allowed to warm to room temperature over 2 hours. The solution is cooled to 0 °C again and 5.00 g (12.7 mmol, 1.0 eq.) l,2:3,4-di-0- isopropylidene-a-D-galactopyranosyltriflate dissolved in 50 ml diethyl ether is added dropwise. The reaction is warmed to ambient temperature and stirred overnight. Wet diethyl ether is added and then the solvent is removed under reduced pressure. The residue is purified by column chromatography (ethyl acetate/n-hexane 1:3 v/v) yielding 3.62 g (7.67 mmol, 60% yield) 1- ( ,2':3',4'-di-0-isopropylidene-6'-deoxy-a-D-galactopyranos-6' -yl)-9-(te/t-butylthio)-l,7- dicarba-c/oso-dodecaborane(12) (17) as a colorless solid oil (Rf-value = 0.50, n-hexane/ethyl acetate = 3/1 v/v).

¹ H-N M R (400 M Hz, CDCI ₃ ): d = 1.30 (s, 3H, C ¹² ' ¹² ’H ₃ ), 1.34 (s, 3H, C ¹³ ' ¹³ ’H ₃ ), 1.41 (s, 3H, C ¹² ' ¹² ’H ₃ ), 1.43 (s, 9H, C(CH ₃ ) ₃ ), 1.50 - 3.50 (br ^a , 9H, BI ₀ H ₉ ), 1.59 (s, 3H, C ¹³ ' ¹³ ’H ₃ ), 2.15 (virtual d, ² 7HH = 15.9 Hz, 1H, C ⁴ H ₂ ), 2.34 (ddd, ² 7 _H H = 16.0 Hz, ³ 7 _H H = 9.0 Hz, ³ 7 _H H = 4.6 Hz, 1H, C ⁴ H ₂ ), 2.96 (br, s, 1H, C ¹⁴ H), 3.77 (ddt, ³ 7 _H H = 8.9 Hz, ³ 7 _HH = 4.4 Hz, ³ 7 _H H = 2.2 Hz, 1H, C ⁵ H), 4.04 (virtual dd, ³ 7HH = 7.8 Hz, 7HH = 1.6 Hz, 1H, C ⁷ H), 4.28 (virtual dd, ³ 7 _H H = 5.1 Hz, 7 _H H = 2.4 Hz, 1H, C ⁸ H), 4.57 (virtual dd, ³ 7 _H H = 7.9 Hz, 7 _H H = 2.2 Hz, 1H, C ⁶ H), 5.52 (d, ³ 7 _H H = 5.1 Hz, 1H, C ⁹ H) ppm. ¹³ C{ ¹ H}-NMR (100 MHz, CDCI ₃ ): d = 23.3, 23.9 and 24.9 (s, 4xCH ₃ of C ¹² H ₃ , C ^12' H ₃ , C ¹³ H ₃ and C ^13' H ₃ ), 31.8 (s, C(CH ₃ ) ₃ ), 37.1 (s, C ⁴ H ₂ ), 43.2 (C _q ² ), 53.8 and 54.0 (s, C ¹⁴ H), 65.9 and 66.0 (s, C ⁵ H), 69.0 (s, C ⁸ H), 69.8 (s, C ⁶ H), 71.5 (s, C _q ³ ), 72.0 (s, C ⁷ H), 95.5 (s, C ⁹ H), 108.1 (s, C _q ¹¹ ), 108.3 (s, C _q ¹⁰ ) ppm.

¹¹ B{ ¹ H}-NMR (128 MHz, CDCI ₃ ): d = -1.4 (s, IB, B ⁹ S), -2.0 to 20.0 (br ^a , 9B) ppm.

B-NMR (128 MHz, CDCI ₃ ): d = -1.4 (s, IB, B ⁹ S), -2.0 to 20.0 (br ^a , 9B) ppm.

I R spectroscopy (KBr, v in cm ¹ ): 2989 (s), 2601 (s, BH), 1457 (m), 1384 (s), 1258 (s), 1213 (s), 1166 (s), 1071 (s), 1003 (s), 899 (m), 858 (m), 738 (m), 510 (m).

Mass spectrometry (HR-ESI, positive mode):

calculated for Ci ₈ H ₃₈ Bio0 ₅ Si: m/z = 475.35254 (int. 100%, [M+H] ⁺ )

found: m/z = 475.35275 (int. 100%, [M+H] ⁺ )

found:

calculated:

Ex 19: l-( ,2':3' _f 4'-Di-0-isopropylidene-6'-deoxy-a-D-galactopyranos-6'- yl)-9-(mercapto)-l,7- dicarba-c/oso-dodecaborane(12)

The following procedure is performed according to the synthesis for the o/tfto-carbaborane derivative [see R. Frank, S. Boehmke, A. Aliev, E. Hey-Hawkins, Polyhedron 39, 9 (2012)].

The reaction was carried out under nitrogen.

0.36 g (0.76 mmol, 1.0 eq.) l-(l',2':3',4'-di-0-isopropylidene-6'-deoxy-a-D-galactopyran os-6'-yl)- 9-(te/t-butylthio)-l,7-dicarba-c/oso-dodecaborane(12) (Ex 17) is dissolved in DCM, transferred to a Schlenk flask and dried in high vacuum. 17 is then dissolved in 3.5 ml dry acetic acid. 0.36 g (1.14 mmol, 1.5 eq.) Hg(OAc) ₂ is added in one portion, resulting in a pale yellow color of the reaction mixture. The reaction mixture is stirred at 50 °C for 3 hours, during which the color turns intensely yellow. The reaction is quenched with 1.6 ml (1.78 g, 22.75 mmol, 20.0 eq.) 2- mercaptoethanol, resulting in a black-greyish precipitate. The suspension is diluted with 100 ml ethyl acetate. The organic phase is two times extracted with 100 ml of a 5% NaHC0 ₃ solution. The resulting aqueous phase is then four times extracted with ethyl acetate, 200 ml each. The combined organic phases are concentrated under reduced pressure and dried over Na ₂ S0 ₄ . After filtration, the solution is further concentrated under reduced pressure to give a suspension, which crystallizes overnight. TLC shows the product with an R _f -value of R _f = 0.47 (n-hexane/ethyl acetate = 3/1 v/v) as an orange spot followed by 2-(acetylthio)ethyl acetate with an R _f -value of R _f = 0.45 as a yellow spot; both change color with a 10% PdCI ₂ solution in methanol. The crude product is purified by column chromatography over silica using an n-hexane/ethyl acetate gradient mixture (3/l:l/l) as eluent, yielding 0.30 g (0.73 mmol, 96%) product as an oily solid.

¹ H-NMR (400 MHz, CDCI ₃ ): d = 2.06 (s, 3H, CH3COO), 2.36 (s, 3H, CH3COS), 3.13 (t, 7 _HH = 6.5 Hz,

2H, CH ₂ S), 4.18 (t, JHH = 6.5 Hz, 2H, CH ₂ 0) ppm.

for comparison see: M. Liras et ai, Polym. Chem., 2013, 4, 5751-5759.

¹ H-NMR (400 MHz, CDCI3): d = 0.43 (m, 1H, SH), 1.30 (s, 3H, 1XCH ₃ , C H ₃ or C ^' H ₃ ), 1.34 (s, 3H, 1XCH ₃ , C ¹² H ₃ or C ^12' H ₃ ), 1.42 (s, 3H, 1XCH ₃ , C H ₃ or C ^' H ₃ ), 1.50 - 3.50 (br ^a , 9H, B10H9), 1.59 and 1.60 (s, 3H, 1XCH ₃ , C ¹² H ₃ or C ^12' H ₃ ), 2.15 (virtual dt, ² 7 _H H = 15.9 Hz, 7 _H H = 2.6 Hz, 1H, C ³ H ₂ ), 2.34 (ddd, ² 7 _H H = 15.9 Hz, ³ 7 _H H = 8.7 Hz, 7 _H H = 3.4 Hz, 1H, C ³ H ₂ ), 2.97 (br, s, 1H, C ¹ H), 3.75 (ddt, ³ 7HH = 8.9 Hz, 7HH = 4.4 Hz, ⁴ 7 _HH = 2.2 Hz, 1H, C ⁴ H), 4.03 (dd, ³ 7 _H H = 7.9 Hz, ⁴ 7 _H H = 2.0 Hz, 1H, C ⁶ H), 4.28 (ddd, ³ 7 _H H = 5.1 Hz, ⁴ 7 _H H = 2.5 Hz, ⁴ 7 _H H = 0.8 Hz, 1H, C ⁷ H), 4.57 (ddd, ³ 7 _H H = 7.8 Hz, ⁴ 7 _H H = 2.5 Hz, ⁴ 7HH = 1.0 Hz, 1H, C ⁵ H), 5.52 (d, ³ 7 _H H = 5.1 Hz, 1H, C ⁸ H) ppm.

¹³ C{ ¹ H}-NMR (100 MHz, CDCI3) : d = 24.4, 24.9, 25.8 and 25.9 (s, 4xCH ₃ : C H ₃ , C ^' H ₃ , C ¹² H ₃ , C ^12' H ₃ ), 37.9 and 38.0 (s, both C ³ H ₂ ), 54.8 (br, s, C ¹ H), 68.0 and 67.0 (s, both C ⁴ H), 70.0 (C ⁷ H), 70.8 (C ⁵ H), 73.05 and 73.07 (s, both C ⁶ H), 73.5 (br, s, C _q ² ), 96.6 (s, C ⁸ H), 108.70 and 108.73 (s, both C _q ¹⁰ ), 109.3 (s, both C _q ⁹ ) ppm.

¹¹ B{ ¹ H}-NMR (128 MHz, CDCI ₃ ): d = -2.6 (s, IB, B ⁹ S), -5.0 to -22.0 (br ^a , 9B) ppm.

B-NMR (128 MHz, CDCI ₃ ): d = -2.6 (s, IB, B ⁹ S), -5.0 to -22.0 (br ^a , 9B) ppm.

IR spectroscopy (KBr, v in cm ^-1 ): 3446 (br, m), 3051 (m), 2990 (s), 2937 (m), 2600 (s, BH), 1456 (w), 1428 (w), 1384 (s), 1257 (m), 1213 (m), 1166 (m), 1107 (m), 1070 (s), 1003 (m), 899 (m), 856 (m), 758 (m), 668 (w), 509 (w).

Mass spectrometry (HR-ESI, positive mode):

calculated for C14H30B10O5S1: m/z = 419.28960 (int. 100%, [M] ⁺ )

found: m/z = 419.28976 (int. 100%, [M] ⁺ ) Elemental analysis:

Calculated for C14H30B10O5S1: C = 40.18% H = 7.22%; found: C = 39.35% H = 7.40% found: calculated:

Ex 20: l-i ^B'^'-Di-O-isopropylidene-e'-deoxy-a-D-galactopyranos-e'-y -g-icarboxymethyl- thio)-l,7-dicarba-c/oso-dodecaborane(12)

The following procedure is performed according to the synthesis for the orf/70-carbaborane derivative [see R. Frank, S. Boehnke, A. Aliev, E. Hey-Hawkins, Polyhedron 39, 9 (2012)].

The reaction was carried out under nitrogen.

0.20 g (0.48 mmol, 1.0 eq.) l-(l',2':3',4'-Di-0-isopropylidene-6'-deoxy-a-D-galactopyran os-6'-yl)- 9-(mercapto)-l,7-dicarba-c/o50-dodecaborane(12) (Ex 19) is dissolved in DCM, transferred to a Schlenk flask and dried in high vacuum. 0.27 g (1.43 mmol, 3.0 eq.) iodoacetic acid is added. The flask is evaporated and filled again with nitrogen. Then the contents is dissolved in 7 ml dry DCM. With stirring 0.46 ml (0.34 g, 3.33 mmol, 7.0 eq.) dry triethylamine is added in one portion at ambient temperature. The mixture is stirred at ambient temperature for 3 days. The reaction mixture is cooled to 0 °C, quenched with ca. 10 ml of a 2 N HCI solution and stirred for 30 seconds. The phases are separated and the aqueous phase is first extracted two times with 10 ml ethyl acetate each and then three times with 20 ml ethyl acetate each. The combined organic phases are dried over Na ₂ S0 ₄ at 0 °C. After filtration, the solution is dried under reduced pressure. The raw product is purified by column chromatography on silica using an n-hexane/ethyl acetate gradient mixture (1/1:0/1) as eluent, yielding 0.11 g (0.24 mmol, 50%) of white oily solid.

!H-NMR (400 MHz, CDCI3): 5 = 1.30 (s, 3H, 1XCH ₃ , C ¹² H ₃ or C ¹² H ₃ ), 1.34 (s, 3H, 1XCH ₃ , C ¹³ H ₃ or C ^13' H ₃ ), 1.42 (s, 3H, 1XCH ₃ , C ¹² H ₃ or C ^12' H ₃ ), 1.50 - 3.50 (br ^a , 9H, B ₁₀ H ₉ ), 1.587 and 1.593 (s, 3H, 1XCH ₃ , C ¹³ H ₃ or C ^13' H ₃ ), 2.14 (virtual dt, ² 7 _HH = 15.9 HZ, 7 _H H = 2.5 HZ, lH, C ⁴ H ₂ ), 2.35 (ddd, I/HH = 16.1 Hz, 7H H = 9.2 Hz, 7HH = 2.0 Hz, 1H, C ⁴ H ₂ ), 2.99 (br, s, 1H, C ¹⁴ H), 3.38 (d, 7HH = 5.2 Hz, 2H, C ² H ₂ ) 3.74 (m, 1H, C ⁵ H), 4.03 (m, 1H, C ⁷ H), 4.29 (virtual dd, ³ 7 _HH = 5.1 Hz, ⁴ 7 _H H = 2.5 Hz, 1H, C ⁸ H), 4.58 (virtual dd, 7 _HH = 7.9 Hz, ⁴ 7 _HH = 2.4 Hz, 1H, C ⁶ H), 5.53 (d, ³ 7 _HH = 5.1 Hz, 1H, C ⁹ H), 8.45 (br, s, 1H, COOH) ppm. ¹³ C{ ¹ H}-NMR (100 MHz, CDCI ₃ ): d = 24.4, 24.9, 25.85 and 25.93 (s, 4xCH ₃ : C ¹² H ₃ , C ^12' H ₃ , C ¹³ H ₃ , C ^13' H ₃ ), 34.5 (s, C ² H ₂ ), 38.0 (s, C ⁴ H ₂ ), 54.4 (s, C ¹⁴ H), 67.0 (s, C ⁵ H), 70.0 (s, C ⁸ H), 70.9 (s, C ⁶ H), 73.1 (s, C ⁷ H), 73.2 (s, C _q ³ ), 96.6 (s, C ⁹ H), 108.7 and 108.8 (both C _q ¹¹ ), 109.4 (s, C _q ¹⁰ ), 174.2 (s, C _q ¹ ) ppm.

¹¹ B{ ¹ H}-NMR (128 MHz, CDCI ₃ ): d = -0.8 (s, IB, B ⁹ S), -2.0 to -20.0 (br ^a , 9B) ppm.

B-NMR (128 MHz, CDCI ₃ ): d = -0.8 (s, IB, B ⁹ S), -2.0 to -20.0 (br ^a , 9B) ppm.

IR spectroscopy (KBr, v in cm ¹ ): 3053 (s), 2990 (s), 2936 (s), 2602 (s, BH), 1712 (s, COOH), 1457 (m), 1428 (m), 1385 (s), 1303 (m), 1259 (s), 1213 (s), 1166 (s), 1142 (m), 1107 (s), 1069 (s), 1003 (s), 955 (m), 919 (m), 898 (m), 855 (m), 802 (m), 774 (m), 740 (m), 668 (w), 645 (w), 534 (w), 509 (m), 460 (w).

Mass spectrometry (HR-ESI, positive mode):

calculated for Ci ₆ H ₃₂ Bi ₀ NaiO ₇ Si: m/z = 499.27728 (int. 100%,[M+Na] ⁺ )

found: m/z = 499.27684 (int. 100%,[M+Na] ⁺ )

Elemental analysis:

calculated for CI ₆ H ₃₂ BI ₀ O ₇ SI: C = 40.32% H = 6.77%;

found: C = 40.05% H = 6.67%

found:

calculated:

Ex 21: l _f 7-[Bis(l' _f 2':3',4'-di-0-isopropylidene-6'-deoxy-a-D-galactopyran os-6'-yl)]-9-(carboxy- methylthio)-l,7-dicarba-c/oso-dodecaborane(12)

n-Butyllithium (2.84 ml of a 1.45 M n-hexane solution, 4.12 mmol, 2.1 eq.) is added dropwise at 0 °C to a solution of 0.46 g (1.96 mmol, 1.0 eq.) 9-(carboxymethylthio)-l,7-dicarba-c/oso- dodecaborane(12) (Ex 11) in 100 ml THF. The suspension is warmed to room temperature over 2 hours. The solution is then cooled again to 0 °C and 771 mg (5.62 mmol, 1.0 eq.) l,2:3,4-di-0- isopropylidene-6-deoxy-a-D-galactopyranosyl-6-triflate (Ex 14) is added. The solution is warmed to room temperature, stirred overnight and quenched with distilled water and saturated sodium hydrogen carbonate solution. The aqueous phase is acidified with diluted HCI and extracted 5 times with 20 ml diethyl ether. The combined organic phases are washed with 50 ml brine, dried over magnesium sulfate and the solvent is removed under reduced pressure. The residue is purified by chromatography (with Isolera 4).

Yield: 30 mg (0.04 mmol, 10%))

R _f -value: 0.10 (eluent: n-hexane/ethyl acetate 1:2 v/v)

¹ H-NMR (400 MHz, CDCI ₃ ): d = 1.18 - 3.31 (br ^a , 9H, BioHg), 1.31 (s, 6H, C ⁸ H ₃ ), 1.33 (s, 6H, C ¹² H ₃ ), 1.41 (s, 6H, C ⁸ H ₃ ), 1.57 and 1.58 (s, 6H, C ¹² H ₃ ), 2.18 (ddd, ² 7 _H H = 15.8 Hz, ³ 7 _H H = 3.0 Hz, 2H, C ⁴ H _2a ), 2.33 (virtual dd, ² 7 _H H = 15.8 Hz, ³ 7 _H H = 8.5 Hz, 2H, C ⁴ H _2b ), 3.39 (s, 2H, C ² H ₂ ), 3.70 (br d, ³ 7 _H H = 8.2 Hz, 2H, C ⁵ H), 4.06 and 4.08 (virtual t, ³ 7 _H H = 8.1 Hz, 2H, C ⁶ H), 4.28 (dd, ³ 7 _H H = 5.1 Hz, ³ 7 _H H = 2.3 Hz, 2H, C ¹⁰ H), 4.58 (virtual dd, ³ 7 _H H = 7.8 Hz, ³ 7 _H H = 2.3 Hz, 2H, C ⁹ H), 5.49 (d, ³ 7 _H H = 5.1 Hz, 2H, C ¹³ H) ppm.

¹¹ B{ ¹ H}-NMR (128 MHz, CDCI ₃ ): d = -1.3 (s, IB), -2.0 to -20.0 (br ^a , 9B) ppm.

¹³ C{ ¹ H}-NMR (100 MHz, CDCI ₃ ): d = 24.2 (s, C ⁸ ' ¹² H ₃ ), 24.8 (s, C ⁸ ' ¹² H ₃ ), 25.7 (s, C ⁸ ' ¹² H ₃ ), 25.8 (s, C ⁸ ' ¹² H ₃ ), 34.6 (s, C ² H), 37.7 (s, C ⁴ H), 66.8 (s, C ⁵ H), 70.0 (s, C ¹⁰ H), 70.7 (s, C ⁹ H), 72.67 and 72.69 (s, both C ⁶ H), 73.0 (s, C _q ³ ), 96.4 (s, C ¹³ H), 108.62 and 108.64 (s, both C _q ¹¹ ), 109.2 (s, C _q ⁷ ), 171.3 (s, Cq ¹ ) ppm. Mass spectrometry (LR-ESI, negative mode, CH2CI2/CH ₃ OH): calculated for C H B O S : m/z = 719.5 found: m/z = 718.5 (100% [M-H] ), 1436.9 (30% [2M— H] )

Ex 17b: l^-Bis-ll'^'iS'^'-Di-O-isopropylidene-e'-deoxy-a-D-galactopy ranos-e'-yl^-iferf- butylthio)-l,7-dicarba-c/oso-dodecaborane(12)

3.00 g (12.91 mmol, 1.0 equiv) 9-(fe/t-butylthio)-l,7-dicarba-c/o50-dodecaborane(12) is dissolved in 100 ml tetrahydrofuran, cooled to 0 °C and 18.70 ml (1.45 M in /i-hexane, 27.11 mmol, 2.1 equiv) n-butyllithium are added dropwise. The reaction is warmed to room temperature over 2 h. The solution is cooled to 0 °C again and 10.66 g (27.11 mmol, 2.1 equiv) l,2:3,4-di-0-isopropylidene-a-D-galactopyranosyltriflate dissolved in 50 ml tetrahydrofuran are added dropwise. The reaction is warmed to ambient temperature and stirred overnight. Wet tetrahydrofuran is added and then the solvent is removed under reduced pressure. The residue is purified by column chromatography (ethyl acetate/n-hexane 1:3 v/v) yielding 17b as colorless oily solid.

Yield: 4.96 g (6.92 mmol, 54 %)

Rf-value: 0.47 (eluent: n-hexane/ethyl acetate 3:1, v/v)

m.p.: 64-65°C

¹ H-NM R (400 MHz, CDCI ₃ ): 5 = 1.20 - 3.50 (br ^a , 9H, BioHg), 1.32 (s, 6H, 1XCH ₃ , C H ₃ or C ⁿ 'H ₃ ), 1.35 (s, 6H, 1XCH ₃ , C ¹² H ₃ or C ¹² 'H ₃ ), 1.43 (s, 9H, 3xCH ₃ , C^Hg), 1.59 and 1.60 (s, 6H, 1XCH ₃ , C ¹² H ₃ or C ¹² H ₃ ), 2.21 (virtual dt, ² 7 _H H = 15.8 Hz, J _{H H} = 3.5 Hz, 2H, C ³ H ₂ ), 2.31 (ddd, ² 7 _H H = 15.5 HZ, ³ 1HH = 7.8 Hz, JHH = 3.0 Hz, 2H, C ³ H ₂ ), 3.75 (ddt, ³ 1HH = 8.1 Hz, J _H H = 5.8 Hz, ⁴ 7 _HH = 2.3 Hz, 2H, C ⁴ H), 4.12 (dt, ³ VHH = 7.8 Hz, ⁴ J _H H = 2.6 Hz, 2H, C ⁶ H), 4.29 (dd, ³ 1 _H H = 5.2 Hz, ⁴ 7 _HH = 2.3 Hz, 2H, C ⁷ H), 4.57 (dd, ³ 7 _H H = 8.1 Hz, ⁴ 7 _H H = 2.3 Hz, 2H, C ⁵ H), 5.52 (d, ³ J _m = 5.1 Hz, 2H, C ⁸ H) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, CDCI ₃ ): d = 24.2, 24.8, 25.8 and 25.9 (s, 8xCH ₃ : C ¹² H ₃ , C ^12' H ₃ , C ¹³ H ₃ , C ^13' H ₃ ), 32.7 (s, ⁽ !¾), 37.8 (s, C ⁴ H ₂ ), 44.1 (s, C ³ _q ), 66.78 and 66.82 (s, both C ⁸ H), 70.0 (s, C ⁷ H), 70.7 (s, C ⁵ H), 71.9 and 72.1 (s, C ² _q ), 72.58 and 72.60 (s, both C ⁶ H), 96.4 (s, C ⁹ H), 108.6 (s, C _q ¹⁰ ), 109.1 (s, C _q ¹¹ ) ppm.

¹¹ B{ ¹ H}-NMR (128 MHz, CDCI ₃ ): d = -1.0 (s, IB, B ⁹ S), -5.0 to -22.0 (br ^a , 9B) ppm.

IR spectroscopy (KBr, v in cm ^-1 ): 3445 (s), 2964 (w), 2596 (m, BH), 1635 (m), 1382 (m), 1258 (m), 1213 (m), 1167 (m), 1144 (m), 1070 (s), 1031 (m), 1003 (m), 857 (w), 802 (w), 642 (w).

Mass spectrometry (HR-ESI, positive mode):

calculated for CsoHseBioOioSNa: m/z = 740.4459 (int. 100%, [M+Na] ⁺ )

found: m/z = 740.4460 (int. 100%, [M+Na] ⁺ )

found (Figure 2):

Elemental analysis:

Calculated for C30H56B10O10S1: C = 50.26% H = 7.87%;

found: C = 43.46% H = 7.43%

Ex 19b: l^-Bis-i ^'iS'^'-Di-O-isopropylidene-S'-deoxy-a-D-galactopyranos-e'-y -S-

(mercapto)-l,7-dicarba-c/oso-dodecaborane(12)

4.92 g (6.90 mmol, 1.0 equiv) of 17b is dissolved in 50 ml dry acetic acid. 3.30 g (10.35 mmol, l.5 equiv) Hg(OAc)2 is added in one portion, resulting in a pale yellow color of the reaction mixture. The reaction mixture is stirred at 50 °C for 3 h, during which the color turns intensely yellow. The reaction is cooled to room temperature, 100 ml degassed ethyl acetate are added and hydrogen sulfide is bubbled through the solution over 20 min resulting in a black precipitate. The suspension is filtered, nitrogen is bubbled through the filtrate to remove hydrogen sulfide and the filtrate is washed two times with 50 ml of a 5 % NaHC03 solution. The orga nic phase is dried over MgS0 ₄ and then the solvent is removed under reduced pressure. The residue is purified by column chromatography on mercapto-propyl coated silica* yielding 19b as a colorless oily solid.

Yield: 4.60 g (6.72 mmol, 97 %)

Rf-value: 0.62 (eluent: n-hexane/ethyl acetate 2:1 v/v)

m.p.: 70-71 °C

^! H-N M R (400 MHz, CDCIs): d = 0.43 (m, 1H, SH), 1.16 - 3.51 (br ^a , 9H, BioHg), 1.33 (s, 6H, lxCHs, C H ₃ or C ^n' H ₃ ), 1.35 (s, 6H, 1XCH ₃ , C ¹² H ₃ or C ^12' H ₃ ), 1.43 (s, 6H, 1XCH ₃ , C H ₃ or C ^n' H ₃ ), 1.60 and 1.61 (s, 6H, 1XCH ₃ , C ¹² H ₃ or C ¹² 'H ₃ ), 2.22 (virtual dt, ² 7 _H H = 15.9 Hz, Jm = 2.6 Hz, 2H, C ³ H ₂ ), 2.32 (ddd, ² VHH = 15.9 Hz, 1/ _H H = 8.7 Hz, JHH = 3.4 Hz, 2H, C ³ H ₂ ), 3.75 (ddt, ³ V _H H = 8.9 Hz, 7 _H H = 4.4 Hz, ⁴ 7 _{H H} = 2.2 Hz, 2H, C ⁴ H), 4.10 (dd, ³ 7 _H H = 7.9 Hz, ⁴ 7 _H H = 2.0 Hz, 2H, C ⁶ H), 4.28 (ddd, ³ 7 _H H = 5.1 Hz, ⁴ 7HH = 2.5 Hz, ⁴ VHH = 0.8 Hz, 2H, C ⁷ H), 4.57 (ddd, I/HH = 7.8 Hz, ⁴ VHH = 2.5 Hz, ⁴ JHH = 1.0 Hz, 2H, C ⁵ H), 5.52 (d, ³ VHH = 5.1 Hz, 2H, C ⁸ H) ppm.

^C^HJ-NM R (100 M Hz, CDCIs): d = 24.3, 25.0, 25.8 and 25.9 (s, 8xCH ₃ : C ⁿ H ₃ , C ¹¹ H ₃ , C ¹² H ₃ , C ¹² H ₃ ), 37.9 and 38.0 (s, both C ³ H ₂ ), 60.4 (br, s, C ² _q ), 66.9 and 67.0 (s, both C ⁴ H), 70.0 (C ⁷ H), 70.8 (C ⁶ H), 72.7 and 72.8 (s, both C ⁵ H), 96.5 (s, C ⁸ H), 108.70 and 108.73 (s, both C _q ¹⁰ ), 109.22 and 109.24 (s, both Cq ⁹ ) ppm.

“B^HJ-NMR (128 MHz, CDCI ₃ ): d = -2.8 (s, IB, B ⁹ S), -4.0 to -22.0 (br ^a , 9B) ppm.

IR spectroscopy (KBr, v in cm ¹ ): 3446 (br, m), 2989 (m), 2934 (s), 2606 (m, BH), 1633 (w), 1457 (w), 1382 (s), 1257 (s), 1213 (s), 1169 (m), 1107 (m), 1070 (s), 918 (m), 900 (m), 884 (m), 862 (m), 804 (w), 756 (w), 648 (w), 553 (w), 511 (w).

Mass spectrometry (HR-ESI, positive mode):

calculated for C14H30B10O5S1: m/z = 684.3833 (int. 100%, [M+Na] ⁺ )

found: m/z = 684.3820 (int. 100%, [M+Na] ⁺ )

found:

Elemental analysis:

Calculated for CzeH^BioOioSi: C = 47.26% H = 7.32%;

found: C = 43.96% H = 7.21%

[*] E. Svantesson, J. Pettersson, A. Olin, K. Markides, S. Sjoberg, A. Tallec, T. Shono, H. Toftlund, Acta Chem. Scand. 1999, 53, 731-736.

Ex 20b: l^-Bis-i ^B'^'-Di-O-isopropylidene-e'-deoxy-a-D-galactopyranos-e'-yll -O- (carboxymethyl-thio)-l,7-dicarba-c/oso-dodecaborane(12)

The synthesis of building block 20b from 19b is performed according to the procedure for building block 20.

Yield: 1.06 g (1.43 mmol, 47 %)

R _f -value: 0.38 (eluent: n-hexane/ethyl acetate 1:1 v/v)

m.p.: 94-95 °C

^! H-N M R (400 MHz, CDCIs): d = 1.31 (s, 6H, C ⁸ H ₃ ), 1.33 (s, 6H, C ¹² H ₃ ), 1.41 (s, 6H, C ⁸ H ₃ ), 1.57 a nd 1.58 (s, 6H, C ¹² H ₃ ), 1.59 - 3.47 (br ^a , 9H, B10H9), 2.22 (ddd, ² VHH = 15.8 Hz, ³ VHH = 3.0 Hz, 2H, C ⁴ H _2a ), 2.31 (virtual dd, ² 7 _H H = 15.8 Hz, ³ V _H H = 8.5 Hz, 2H, C ⁴ H _2b ), 3.38 (s, 2H, C ² H ₂ ), 3.70 (br d, ³ V _H H = 8.2 Hz, 2H, C ⁵ H), 4.07 and 4.09 (virtual t, ³ J _H H = 8.1 Hz, 2H, C ⁶ H), 4.28 (dd, ³ J _H H = 5.1 Hz, ³ V _H H = 2.3 Hz, 2H, C ¹⁰ H), 4.56 (virtual dd, ³ J _H H = 7.8 Hz, 1/ _H H = 2.3 Hz, 2H, C ⁹ H), 5.49 (d, ³ 7 _H H = 5.1 Hz, 2H, C ¹³ H) ppm.

“B^Hj-NM R (128 M Hz, CDCI ₃ ): d = -1.1 (s, IB), -2.0 to -20.0 (br ^a , 9B) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, CDCI ₃ ): 6 = 24.3 (s, C ⁸ ' ¹² H ₃ ), 24.9 (s, C ^{8 12} H ₃ ), 25.8 (s, C ⁸ ' ¹² H ₃ ), 25.9 (s, C ⁸ ' ¹² H ₃ ), 34.5 (s, C ² H), 37.8 (s, C ⁴ H), 66.9 (s, C ⁵ H), 70.0 (s, C ¹⁰ H), 70.8 (s, C ⁹ H), 72.67 and 72.69 (s, both C ⁶ H), 73.0 (s, C _q ³ ), 96.5 (s, C ¹³ H), 108.62 and 108.64 (s, both C _q ⁿ ), 109.2 (s, C _q ⁷ ), 171.2 (s, Cq ¹ ) ppm.

I R spectroscopy (KBr, v in cm ^-1 ): 3445 (br, m), 2989 (m), 2936 (m), 2596 (m, BH), 1714 (m), 1636 (w), 1457 (w), 1426 (w), 1383 (m), 1257 (m), 1213 (s), 1168 (m), 1107 (m), 1070 (s), 1003 (m), 919 (w), 898 (m), 803 (w), 774 (m), 648 (w), 511 (w).

Mass spectrometry (HR-ESI, positive mode):

calculated for C ₂₈ H ₅ oBi ₀ Oi ₂ SNa: m/z = 742.3888 (100 % [M+Na] ⁺ )

found: m/z = 742.3901 (100% [M+Na] ⁺ ). found:

Elemental analysis:

Calculated for C28H50B10O12S1: C = 46.78% 1-1 = 7.01%; found: C = 46.51% 1-1 = 7.14%

Ex 34: l-( ,2':3',4'-Di-0-isopropylidene-6'-cleoxy-a-L-galactopyranos-6 '-yl)-9-(carboxymethyl- thio)-l,7-dicarba-c/oso-dodecaborane(12)

The synthesis is analogous to the corresponding compound (Ex 20) with a D-configuration of the galactopyranosyl substituent, with l,2:3,4-di-0-isopropylidene-6-deoxy-a-i_-galactopyranosyl-6- triflate as starting material.

^! H-NMR (400 MHz, CDCI ₃ ): d = 1.30 (s, 3H, 1XCH ₃ : C ¹² H ₃ or C ^12' H ₃ ), 1.34 (s, 3H, 1XCH ₃ : C ¹³ H ₃ or C ^13' H ₃ ), 1.42 (s, 3H, 1XCH ₃ : C ¹² H ₃ or C ^12' H ₃ ), 1.586 and 1.592 (s, 3H, 1XCH ₃ : C ¹³ H ₃ or C ^13' H ₃ ), 1.70 - 3.50 (br ^a , 9H, BioHg), 2.17 (virtual dt, ² VHH = 16.0 Hz, VHH = 2.6 Hz, 1H, C ⁴ H ₂ ), 2.34 (ddd, ² 7HH = 15.9 Hz, J _H H = 9.2 Hz, J _{H H} = 2.3 Hz, 1H, C ⁴ H ₂ ), 2.97 (br, s, 1H, C ¹⁴ H), 3.38 (virtual d, 7HH = 3.9 Hz, 2H, C ² H ₂ ) 3.75 (m, 1H, C ⁵ H), 4.05 (m, 1H, C ⁷ H), 4.28 (virtual dd, ³ 7 _HH = 5.1 HZ, ⁴ 7HH = 2.4 Hz, 1H, C ⁸ H), 4.56 (virtual dd, J _{H H} = 7.9 Hz, ⁴ J _H H = 2.4 Hz, 1H, C ⁶ H), 5.52 (d, ³ 7 _H H = 5.1 Hz, 1H, C ⁹ H), 10.16 (br, s, 1H, COOH) ppm.

^C^Hj-NMR (100 MHz, CDCI ₃ ): d = 24.3, 24.9, 25.8 and 25.9 (s, 4XCH ₃ : C ¹² H ₃ , C ^12' H ₃ , C ¹³ H ₃ , C ^13' H ₃ ), 34.4 (s, C ² H ₂ ), 38.0 (s, C ⁴ H ₂ ), 53.9 and 54.1 (s, both C ¹⁴ H), 66.94 and 66.97 (s, both C ⁵ H), 69.9 (s, C ⁸ H), 70.8 (s, C ⁶ H), 72.5 (s, C ⁷ H), 73.0 (s, C _q ³ ), 96.5 (s, C ⁹ H), 108.71 and 108.74 (s, both Cq ¹¹ ), 109.2 (s, C _q ¹⁰ ), 175.6 (s, C _q ¹ ) ppm.

“BOHJ-NMR (128 MHz, CDCI ₃ ): d = -0.7 (s, IB, B ⁹ S), -2.0 to -20.0 (br ^a , 9B) ppm.

nB-NMR (128 MHz, CDCI ₃ ): d = -0.7 (s, IB, B ⁹ S), -2.0 to -20.0 (br ^a , 9B) ppm.

IR spectroscopy (KBr, v in cm ¹ ): 3054 (w), 2989 (m), 2936 (w), 2612 (s, BH), 1713 (s, COOH), 1427 (w), 1383 (m), 1301 (w), 1257 (m), 1212 (m), 1166 (m), 1143 (m), 1107 (w), 1069 (m), 1004 (m), 957 (m), 919 (w), 901 (m), 879 (m). Mass spectrometry (HR-ESI, positive mode):

calculated for CieHszBioNaiOySi: m/z = 499.27728 (int. 100%,[M+Na] ⁺ ) found: m/z = 499.27684 (int. 100%,[M+Na] ⁺ )

ferf-Butyl(4,6-dichloro-l,3,5-triazin-2-yl)glycinate

A 250 mL round-bottom flask is charged with 2.02 g (11.0 mmol, 1.00 eq.) cyanuric chloride and is then evacuated and nitrogen-purged. The starting material is dissolved in 80 mL tetrahydrofuran, cooled to -10 °C and 1.23 mL (0.94 g, 7.25 mmol, 0.66 eq.) diisopropylethylamine are added. Then 1.88 g (11.0 mmol, 1.00 eq.) fert-butyl glycinate hydrochloride and 2.47 mL (1.87 g, 14.5 mmol, 1.33 eq.) diisopropylethylamine are suspended in 30 mL tetrahydrofuran and added slowly to the reaction mixture at -10 °C. The mixture is stirred for one more hour at -10 °C and then for two days at room temperature. The reaction is stopped by adding 50 mL of water. After addition of 50 mL of a saturated sodium chloride solution the aqueous phase is separated from the organic one and is extracted three times with 60 mL diethyl ether. The combined organic phases are washed with 50 mL saturated sodium chloride solution, dried over magnesium sulfate, filtered off and the organic solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n-hexane, 1:3 to 1:2, v/v) 2.50 g (8.96 mmol, 81.8%, R/= 0.61, ethyl acetate/n-hexane, 1:2, v/v) of the title compound is obtained as a slightly yellow solid. terf-Butyl(4,6-dichloro-l,3,5-triazin-2-yl)glycinate is an slightly yellow solid which is very soluble in common organic solvents like acetone, acetonitrile, dichloromethane, tetrahydrofuran and chloroform. It is stable at room temperature and can be stored at ambient conditions. The two chloride substituents readily undergo substitution reactions under elevated temperature under basic conditions. Due to the mesomeric effect of the attached triazine moiety, the

nucleophilicity of the amine group 5 is highly decreased and it isn't possible to substitute the proton on position 5 with an electrophile.

^! H-NMR (400 MHz, (CD ₃ ) ₂ CO): d = 1.46 (s, 9H, C^Hak), 4.13 (d, 1/HH = 6.2 Hz, 2H, C ⁴ H ₂ ), 8.15 (vbr, t ³ 7 _HH = 7.0 Hz, 1H, N ⁵ H) ppm.

¹³ C{ ¹ H}-NMR (100 MHz, (CD ₃ ) ₂ CO): d = 28.1 (s, CfC^a), 44.2 (s, C ⁴ H ₂ ), 82.3 (s, C _q ² (CH ₃ ) ₃ ), 167.5 (s, C _q ⁶ ), 168.4 (s, C _q ³ 0), 170.6 (s, C _q ⁷ CI), 171.1 (s, C _q ⁷ CI) ppm. Mass spectrometry (HR-ESI, positive mode, CH2CI2/CH ₃ CN):

calculated for CgHwCblVUNaiC : m/z = 301.02352 ([M+Na] ⁺ ) found: m/z = 301.02354 ([M+Na] ⁺ )

Ex 32: fert-Butyl-/V-(4 _f 6-dichloro-l _f 3 _f 5-triazin-2-yl)-/\/-(l' _f 2 ^, :3' _f 4 ^, -di-0-isopropylidene-6'-deoxy-a- D-galactopyranos-6'-yl)glycinate (32)

A 100 mL Schlenk flask is charged with 1.55 g (3.95 mmol, 1.00 eq.) l,2:3,4-di-0-isopropylidene- 6-deoxy-a-D-galactopyranosyl-6-triflate (14) and 0.80 g (4.77 mmol, 1.21 eq.) tert-butyl glycinate hydrochloride, evacuated, nitrogen-purged and dissolved in 40 mL acetonitrile. Subsequently 2.00 mL (1.52 g, 11.8 mmol, 2.47 eq.) diisopropylethylamine are slowly added at room temperature to the mixture and the mixture is allowed to stir for two days at 45 °C. A solution of 1.83 g (9.92 mmol, 2.51 eq.) cyanuric chloride and 0.87 mL (0.66 g, 5.12 mmol, 1.30 eq.) diisopropylamine in 10 mL acetonitrile is slowly added at 0 °C and the reaction mixture is stirred for two days at 35 °C. The reaction is stopped by adding 50 mL of a saturated sodium chloride solution; the resulting layers are separated. The aqueous phase is extracted three times with 50 mL ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n-hexane, 1:5, v/v) 1.59 g (3.05 mmol, 77.2%, R/ = 0.37) of the title compound is obtained as a slightly yellow solid. terf-Butyl-A/-(4,6-dichloro-l,3,5-triazin-2-yl)-A/-(l',2':3' ,4'-di-0-isopropylidene-6'-deoxy-a-D- galactopyranos-6'-yl)glycinate is a slightly yellow solid and stable under ambient conditions at room temperature. It shows high solubility in common organic solvents like tetrahydrofuran, acetone, acetonitrile and dichloromethane. It is not soluble in water. The solubility in water without all three protective groups wasn't determined. It crystalizes well from concentrated chloroform solution. The two remaining chloride atoms could be easily substituted by nucleophiles under basic conditions and elevated temperatures.

^! H-NM R (400 MHz, CDCIs): d = 1.31 (s, 3H, C ¹⁵ ' ¹⁵ 'H ₃ ), 1.34 (s, 3H, C ¹⁶ ' ¹⁶ 'H ₃ ), 1.44 (s, 3H, C ¹⁵ ' ¹⁵ 'H ₃ ), 1.47 (s, 9H, C^H^s), 1.50 (s, 3H, C ^{16 16} H ₃ ), 3.68 (dd, ² 7 _H H = 14.3 Hz, ³ 7 _H H = 8.1 Hz, 1H, C ⁷ HH), 3.88 (dd, ² JH = 14.3 Hz, ³ VHH = 5.1 Hz, 1H, C ⁷ HH), 4.19 (d, ² J _H H = 17.5 Hz, 1H, C ⁴ HH), 4.21 (m, 1H, C ⁸ H), 4.26 (dd, I/HH = 7.9 Hz, I/HH = 1.8 Hz, 1H, C ¹⁰ H), 4.30 (dd, I/HH = 5.0 Hz, I/HH = 2.5 Hz, 1H, C H), 4.44 (d, ² VHH = 17.5 Hz, 1H, C ⁴ H), 4.62 (dd, ³ 7 _H H = 7.9 Hz, 1/ _H H = 2.5 Hz, 1H, C ⁹ H), 5.49 (d, ³ 7 _H H = 4.9 Hz, 1H, C ¹² H) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, CDCI ₃ ): d = 24.4, 25.0, 25.9 and 26.0 (s, 4xCH ₃ of C ¹⁵ H ₃ , C ¹⁵ 'H ₃ , C ¹⁶ H ₃ and C ^16' H ₃ ), 28.0 (s, Cf^Hsfe), 50.1 (s, C ⁷ H ₂ ), 52.2 (s, C ⁴ H ₂ ), 65.3 (s, C ⁸ H), 70.5 (s, C ⁿ H), 70.7 (s, C ⁹ H), 71.1 (s, C ¹⁰ H), 82.4 (s, C _q ² ), 96.3 (s, C ¹² H), 108.9 (s, C _q ¹⁴ ), 109.5 (s, C _q ¹³ ), 165.5 (s, C _q ⁵ N), 167.5 (s, C _q , 2xC ⁶ CI), 169.9 (s, Cq, C ³ 0) ppm.

Crystallographic data Empirical formula C21 H30 CI2 N4 07 Formula weight 521.39 Temperature 130(2) K Wavelength 71.073 pm Crystal system Monoclinic Space group P 21 Unit cell dimensions a = 1101.39(2) pm 0= 90°. b = 2213.85(3) pm 0= 105.800(2)°. c = 1132.11(2) pm 0 = 90°.

Volume 2.65614(8) nm ³

Z 4

Density (calculated) 1.304 Mg/m ³

Absorption coefficient 0.289 mm l F(000) 1096

Crystal size 0.40 x 0.20 x 0.15 mm ³

Theta range for data collection 1.840 to 32.262°. I ndex ranges -15<=h<=16, -33<=k<=33, -16<=l<=16

Reflections collected 46570 I ndependent reflections 17504 [R(int) = 0.0341]

Completeness to theta = 30.510° 100.0 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 1.00000 and 0.88446

Refinement method Full-matrix least-squares on

Data / restraints / parameters 17504 / 7 / 853

Goodness-of-fit on F^ 1.020

Final R indices [l>2sigma(l)] Rl = 0.0390, wR2 = 0.0649

R indices (all data) Rl = 0.0590, wR2 = 0.0716

Absolute structure parameter -0.031(13)

Largest diff. peak and hole 0.229 and -0.236 e.A ³

Comments: Structure solution with SHELXT-2014 (dual-space method). Anisotropic refinement of all non-hydrogen atoms with SHELXL-2016. All H atoms were located on difference Fourier maps calculated at the final stage of the structure refinement. Structure determination in accordance with a-D-Galactopyranose derivative.

Hydrogen atoms are omitted for clarity.

Ex 36: ieri-Butyl-/V-[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthi o)-l,3,5-triazin-2-yl]-/V- (r,2':3\4'-di-0-isopropylidene-6'-deoxy-a-D-galactopyranos-6 '-yl)glycinate (36)

A 250 mL two-neck round-bottom flask, equipped with a condenser, is charged with 1.66 g (9.42 mmol, 3.09 eq.) 9-(mercapto)-l,7-dicarba-c/oso-dodecaborane(12) (4) and 1.71 g (12.4 mmol, 4.06 eq.) potassium carbonate, evacuated and nitrogen-purged. The starting materials are suspended in 80 mL acetonitrile. A separate Schlenk flask is charged with 1.59 g (3.05 mmol, 1.00 eq.) ferf-butyl-A/-(4,6-dichloro-l,3,5-triazin-2-yl)-/V-(l',2':3' ,4'-di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)glycinate (32), evacuated, nitrogen-purged and then dissolved in 20 mL acetonitrile. The solution containing the glycinate is added dropwise to the reaction mixture a nd the mixture is then stirred under reflux for three days. The reaction is stopped by adding 50 mL of a saturated aqueous sodium chloride solution. The resulting layers are separated and the aqueous phase is extracted three times with 30 mL ethyl acetate. The combined organic layers are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n-hexane, 1:3, v/v) 1.39 g (1.74 mmol, 57.0%, R/ = 0.25) of the title compound is obtained as a white solid. terf-Butyl-A/-[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthi o)-l,3,5-triazin-2-yl]-/V-(l',2':3',4'-di- 0-isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)glycinate is a white solid which is stable under ambient temperature and atmosphere. The protective groups will be only cleaved in acidic media. In common organic solvents it is not as soluble as its precursor molecules, but soluble enough for further reactions and analytical measurements. The te/t-butyl ester could be selectively cleaved by trifluoroacetic acid in dry dichloromethane, whereas the cleavage of the protective groups at the sugar moiety need aqueous acidic conditions. This compound was crystallized from a mixture of ethyl acetate, n-hexane and acetone.

^! H-N M R (400 MHz, CDCI ₃ ): d = 1.29 (s, 3H, C ¹⁶ ' ^16' H ₃ ), 1.34 (s, 3H, C ^{17 17'} H ₃ ), 1.44 (s, 12H, C ¹⁶ - ^16' H ₃ and C(C ⁷ H ₃ ) ₃ ), 1.46 (s, 3H, C ¹⁷ ' ¹⁷ 'H ₃ ), 1.66 - 3.56 (br ^a , 18H, 2XBI ₀ H ₉ ), 2.96 (br, s, 4H, 4xC ⁴ H), 3.65 (virtual dd, ² 7HH = 14.4 Hz, ³ JHH = 8.2 Hz, 1H, C ⁸ HH), 3.99 (virtual dd, ² 7HH = 14.4 Hz, ³ VHH = 4.6 Hz, 1H, C ⁸ HH), 4.19 (m, 1H, C ⁹ H), 4.26 (m, 2H, C ⁿ ' ¹² H), 4.37 (d, ² 7 _H H = 17.8 Hz, 1H, C ⁴ HH), 4.58 (dd, I/HH = 8.0 Hz, ³ 7HH = 2.4 Hz, 1H, C ¹⁰ H), 4.68 (d, ² 7 _H H = 17.8 Hz, 1H, C ⁴ HH), 5.49 (d, ³ 7 _HH = 5.0 Hz, 1H, C ¹³ H) ppm.

¹¹ B{ ¹ H}-NM R (128 M Hz, CDCI ₃ ): d = -18.7 (s, 2B), -17.4 (s, 2B), -14.0 (s, 4B), -12.8 (s, 4B), -10.0 (s, 2B), -5.6 (s, 4B), -3.1 (s, 2B, 2xBS) ppm.

“B-NM R (128 MHz, CDCI ₃ ): d = -20.5 to -15.8 (br ^a , 4B), -15.4 to -11.4 (br ^a , 8B), -10.0 (d, I/BH = 150 Hz, 2B), -5.6 (d, I/BH = 158 Hz, 4B), -3.1 (s, 2B, 2xBS) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, CDCI ₃ ): d = 24.4, 25.1, 26.0 and 26.1 (s, 4xCH ₃ , C ¹⁶ H ₃ , C ^16' H ₃ , C ¹⁷ H ₃ and C ¹⁷ 'H ₃ ), 28.1 (s, C(C ⁷ H ₃ ) ₃ ), 47.9 (s, C ⁸ H ₂ ), 50.2 (s, C ⁴ H ₂ ), 53.8 (br, s, 4xC ¹ H), 66.4 (s, C ⁹ H), 70.5 (s, C ¹² H), 70.8 (s, C ¹⁰ H), 71.5 (s, C H), 81.4 (s, C _q ⁶ ), 96.3 (s, C ¹³ H), 108.8 (s, C _q ¹⁵ ), 109.2 (s, C _q ¹⁴ ), 163.2 (s, C _q ³ ), 169.3 (s, C _q ² ), 178.5 (s, C _q ⁵ ) ppm.

I R spectroscopy (KBr, v in cm ^-1 ): 3253 (w), 3134 (w), 3064 (m), 3038 (m), 2983 (m), 2952 (m), 2602 (s), 2562 (m), 1967 (w), 1741 (s), 1614 (m), 1534 (s), 1510 (s), 1486 (s), 1421 (m), 1401 (w), 1383 (m), 1370 (s), 1331 (m), 1316 (m), 1301 (m), 1261 (s), 1250 (s), 1222 (s), 1182 (s), 1153 (s), 1102 (s), 1070 (s), 1044 (m), 1007 (s), 976 (m), 952 (s), 919 (w), 901 (m), 879 (w), 864 (m), 848 (s), 803 (m), 772 (w), 757 (w), 731 (m).

Mass spectrometry (HR-ESI, positive mode, (CH ₃ ) ₂ CO): calculated for C ₂₅ H5 ₃ B ₂ oN40 ₇ S ₂ : m/z = 802.53420 ([M+H] ⁺ ) found: m/z = 802.53393 ([M+H] ⁺ )

Elemental analysis: calculated (%) for C25H52B20N4O7S2: C = 37.48, H = 6.54, N = 6.99; found: C = 36.54, H = 6.54, N = 7.12.

Crystallographic data:

Empirical formula C25H52B20N4O7S2

Formula weight 801.02

Temperature 130(2) K

Wavelength 71.073 pm

Crystal system Orthorhombic

Space group P2i2i2i

Unit cell dimensions a = 1018.85(2) pm a = 90°

b = 1675.41(3) pm b = 90° c = 2468.31(5) pm g = 90°

Volume 4.2134(1) nm ³

Z 4

Density (calculated) 1.263 Mg/m ³

Absorption coefficient 0.173 mm ¹

F(000) 1672

Crystal size 0.3 x 0.25 x 0.03 mm ³

Theta range for data collection 2.05 to 30.18°

I ndex ranges -13 < h < 14, -22 < k < 21, -34 < I < 34 Reflections collected 42274

I ndependent reflections 11457 [R(int) = 0.0745]

Completeness to theta = 28.29° 100.0%

Absorption correction Semi-empirical from equivalents Max. and min. transmission l and 0.99061

Refinement method Full-matrix least-squares on F ² Data / restraints / parameters 11457 / 0 / 731 Goodness-of-fit on F ² 1.015

Final R indices [l>2sigma(l)] R1 = 0.0500, wR2 = 0.0754

R indices (all data) R1 = 0.0904, wR2 = 0.0861

Absolute structure parameter 0.08(3)

Largest diff. peak and hole 0.264 and -0.256 e-A ^"3

Comments: Structure solution with SHELXT-2014 (dual-space method). Anisotropic refinement of all non-hydrogen atoms with SHELXL-2014. All H atoms were located on difference Fourier maps calculated at the final stage of the structure refinement.

Hydrogen atoms are omitted for clarity. Ex 37: /V-[4 _f 6-bis(l _l 7-dicarba-c/oso-dodecaboran-9-ylthio)-l _f 3 _f 5-triazin-2-yl]-/V-( _f 2 ^, :3 ^, ,4 ^, -di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)glycine (37)

A 50 mL Schlenk flask is charged with activated molecular sieves (3 A), evacuated and nitrogen- purged. Then 100 mg (125 mitioI, 1.00 eq.) terf-butyl-A/-[4,6-bis(l,7-dicarba-c/oso-dodecaboran- 9-ylthio)-l,3,5-triazin-2-yl]-/V-(l',2':3',4'-di-0-isopropyl idene-6'-deoxy-a-D-galactopyranos-6'- yl)glycinate (36) is added and dissolved in 10 mL toluene. Subsequently, 0.19 mL (285 mg, 2.50 mmol, 20.0 eq.) trifluoroacetic acid is added and the mixture is stirred for three days at 80 °C. The reaction is stopped by adding 5 mL of a saturated aqueous sodium bicarbonate solution. The molecular sieves are filtered off and the two phases are separated. The aqueous phase is extracted three times with 15 mL ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (ethyl acetate, 100%) 45 mg (60.4 pmol, 48.3%, R/ = 0.60) of the title compound is obtained as an off-white solid.

/V-[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5 -triazin-2-yl]-/V-(l',2':3',4'-di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)glycine is an off-white solid and stable under ambient conditions and temperatures. It is soluble in common organic solvents like acetone and dichloromethane. It is also moderately soluble in methanol. Solubility studies with the completely deprotected compound weren't performed yet, but it is assumed that the free acid with the free sugar moiety shows slight water solubility. ⁴ H-NM R (400 Hz, CDCI3): d = 1.28 (s, 3H, C ¹⁴ ' ¹⁴ 'H ₃ ), 1.34 (s, 3H, C ¹⁵ ' ¹⁵ 'H ₃ ), 1.43 (s, 3H, C ¹⁴ ' ¹⁴ 'H ₃ ), 1.46 (s, 3H, C ¹⁵ ' ¹⁵ 'H ₃ ), 1.55 - 3.30 (br ^a , 18H, 2XBI ₀ H ₉ ), 2.98 (br, s, 4H, 4xC ¹ - ¹ 'H), 3.54 (dd, ² J _m = 14.4 Hz, I/HH = 8.4 Hz, 1H, C ⁶ HH), 4.10 (m, 1H, C ⁶ HH), 4.19 (m, 1H, C ⁷ H), 4.27 (m, 2H, C ⁹ - ¹⁰ H), 4.58 (m, 1H, C ⁸ H), 4.64 (br, m, 2H, C ⁴ H ₂ ), 5.48 (d, ³ J _H H = 5.0 Hz, 1H, C ⁿ H), 6.34 (vbr s, 1H, C ⁵ OOH) ppm.

¹¹ B{ ¹ H}-NM R (128 M Hz, CDCI3): d = -19.8 to -4.3 (br ^a , 18B), -3.4 (s, IB, BS), -3.1 (s, IB, BS) ppm. ⁿ B-NM R (128 M Hz, CDCI ₃ ): d = -21.0 to -4.1 (br ^a , 18B), -3.4 (s, IB, BS), -3.1 (s, IB, BS) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, CDCI ₃ ): d = 24.3, 25.1, 26.0 and 26.1 (s, 4xCH ₃ , C ¹⁴ H ₃ , C ¹⁴ 'H ₃ , C ¹⁵ H ₃ and C ^15' H ₃ ), 48.6 (s, C ⁶ H ₂ ), 49.9 (s, C ⁴ H ₂ ), 53.9 (br, s, 2xC ³ H), 54.2 (br, s, 2xC ^1' H), 66.5 (s, C ⁷ H), 70.5 (s, C ¹⁰ H), 70.8 (s, C ⁸ H), 71.5 (s, C ⁹ H), 96.2 (s, C ⁿ H), 108.9 (s, C _q ¹³ ), 109.3 (s, C _q ¹² ), 163.3 (s, C _q ³ ), 175.3 (s, C _q ⁵ ), 178.6 (br, s, C _q ² , 2xCS) ppm.

Mass spectrometry (HR-ESI, positive mode, CHCI3/CH3CN): calculated for C21H45B20N4O7S2: m/z = 746.47131 ([M+H] ⁺ ) found: m/z = 746.47182 ([M+H] ⁺ )

2-Chloro-4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)- l,3,5-triazine

5.00 g (28.4 mmol, 2.00 eq.) 9-(mercapto)-l,7-dicarba-c/oso-dodecaborane(12) and 2.62 g (14.2 mmol, 1.00 eq.) cyanuric chloride are placed in an evacuated and nitrogen-purged 500 mL two-neck round-bottom flask, equipped with a condenser. The starting materials are suspended in 200 mL acetonitrile and cooled to 0 °C. 6.04 mL (4.59 g, 35.5. mmol, 2.50 eq.) diisopropylethylamine are added slowly to this suspension. After 20 minutes stirring at 0 °C the mixture is heated to reflux. After five hours of heating the reaction mixture is cooled to room temperature and stirred overnight at ambient temperatures. The reaction is stopped by adding 20 mL water and 20 mL 2 M hydrochloric acid. Excess acetonitrile is removed under reduced pressure and the remaining aqueous phase is extracted three times with 30 mL ethyl acetate. The combined organic phases are washed with 20 mL of a saturated sodium chloride solution and 20 mL water, respectively. Both aqueous washing solutions are extracted with 50 mL diethyl ether. All combined organic phases are dried over magnesium sulfate, filtered and then the solvent is removed under reduced pressure. The purity of the obtained material proved to be sufficient (by TLC (ethyl acetate/n-hexane, 1:2, v/v). The product was isolated as a slightly yellow solid (quantitative yield, 6.59 g, 14.2 mmol, R/ = 0.63).

2-Chloro-4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)- l,3,5-triazine is a slightly yellow solid which is highly stable under ambient conditions and temperatures. It undergoes substitution reactions at the C-CI group with strong nucleophiles like primary amines or thiolates and is very soluble in common organic solvents like tetrahydrofuran, acetone, acetonitrile or chloroform. It crystallizes well from concentrated chloroform solution.

^! H-NMR (400 MHz, (CD ₃ ) ₂ CO): d = 1.52 - 3.54 (br ³ , 18H, 2XBI ₀ H ₉ S), 3.82 (br, s, 4H, 4xC ¹ H) ppm. “B^HJ-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -18.1 (br, s, 2B), -16.8 (s, 2B), -13.8 (s, 4B), -12.8 (br ^a , 4B), -10.4 (s, 2B), -5.9 (br, s, 4B), -4.0 (s, 2B, 2xBS) ppm. ⁿ B-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -17.5 (br ^a , 4B), -13.2 (br ^a 8B), -10.4 (d, I/BH = 152 Hz, 2B), -5.9 (d, BH = 165 Hz, 4B), -4.0 (s, 2B, 2xBS) ppm.

“C^Hj-NM R (100 M Hz, (CD ₃ ) ₂ CO): d = 56.1 (br, s, 4x0^), 168.5 (s, C _q ³ CI), 182.6 (s, 2xC _q ² S) ppm.

IR spectroscopy (KBr, v in cm ¹ ): 3446 (m), 3072 (m), 3060 (m), 3050 (m), 2962 (w), 2617 (s), 2390 (w), 2091 (w), 1988 (w), 1718 (w), 1624 (w), 1562 (w), 1501 (s), 1477 (s), 1456 (s), 1432 (m), 1312 (m), 1274 (s), 1252 (s), 1166 (m), 1150 (m), 1105 (w), 1067 (m), 1036 (w), 992 (m), 954 (m), 920 (w), 863 (s), 846 (s), 806 (m), 790 (m), 773 (m), 760 (m), 732 (m), 676 (w), 624 (w), 576 (w), 507 (w), 376 (w).

Mass spectrometry (LR-ESI, positive mode, CH2CI2/CH3CN) : calculated for C7H23B20CI1N3S2: m/z = 465.1([M+H] ⁺ ) found: m/z = 465.4 ([M+H] ⁺ ) calculated for C14H46B40CI2UN6S4: m/z = 935.1 (100%, [2M+Li] ⁺ found: m/z = 935.6 (100%, [2M+Li] ⁺

Mass spectrometry (LR-ESI, negative mode, CH2CI2/CH3CN) : calculated for C7H23B20CI2N3S2: m/z = 499.5 ([M+CI] ) found: m/z = 499.3 ([M+CI] )

Elemental analysis: calculated (%) for C7H22B20CI1N3S2: C = 18.12, H = 4.78; found: C = 18.11, H = 4.60. Crystallographic data

Empirical formula C7H22B20CI1N3S2

Formula weight 464.04

Temperature 130(2) K

Wavelength 71.073 pm

Crystal system Monoclinic

Space group P2i/c

Unit cell dimensions a = 1352.87(4) pm a = 90°

b = 1411.68(4) pm b = 98.178(3)° c = 1249.64(5) pm g = 90°

Volume 2.3623(1) nm ³

Z 4

Density (calculated) 1.305 Mg/m ³

Absorption coefficient 0.343 mm ¹

F(000) 936

Crystal size 0.5 x 0.04 x 0.04 mm ³

Theta range for data collection 2.19 to 30.75°

Index ranges -19 < h < 19, -20 < k < 19, -17 < I < 16

Reflections collected 30792

Independent reflections 6750 [R(int) = 0.0598]

Completeness to theta = 28.29° 100.0%

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 1 and 0.96054

Refinement method Full-matrix least-squares on F ²

Data / restraints / parameters 6750 / 0 / 388

Goodness-of-fit on F ² 1.045

Final R indices [l>2sigma(l)] R1 = 0.0486, wR2 = 0.0879 R indices (all data) Rl = 0.0800, wR2 = 0.0975

Extinction coefficient n/a

Largest diff. peak and hole 0.315 and -0.305 e-A ^“3

Comments: Structure solution with SHELXS-2013 (Direct method). Anisotropic refinement of all non-hydrogen atoms with SHELXL-2014. All H atoms were located on difference Fourier maps calculated at the final stage of the structure refinement. With a displacement parameter and bond length analysis the carbaborane carbon atoms C(l), C(2), C(3) and C(4) could clearly be localised.

Hydrogen atoms are omitted for clarity.

2-{[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5 -triazin-2-yl]thio} acetic acid

2.01 g (4.33 mmol, 1.00 eq.) 2-chloro-4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3 ,5- triazine are placed in an evacuated and nitrogen-purged 250 mL two-neck round-bottom flask, equipped with a condenser, and dissolved in 150 mL acetonitrile. 0.45 mL (0.60 g, 6.46 mmol, 1.49 eq.) thioglycolic acid are added to this solution and the mixture is cooled to 0 °C. Then 3.00 mL (2.28 g, 17.6 mmol, 4.07 eq.) diisopropylethylamine are added to this mixture and stirred for 20 minutes. Subsequently, the mixture is wa rmed to room temperature and then stirred for three hours under reflux. The reaction is stopped by adding 30 mL water and 20 mL 2 M hydrochloric acid. All volatile components are removed under reduced pressure and the remaining aqueous phase is extracted two times with 40 mL diethyl ether. The combined organic phases are washed two times with 20 mL water, dried over magnesium sulfate a nd filtered. The organic solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n-hexane, gradient 1:1 to 100% ethyl acetate, v/v) 600 mg (1.15 mmol, 26.6%, R/ = 0.18, 100% ethyl acetate) of the product are isolated as a slightly yellow solid.

2-{[4,6-Bis(l,7-dicarba-c/o50-dodecaboran-9-ylthio)-l,3,5 -triazin-2-yl]thio} acetic acid is a slightly yellow, crystalline solid and stable at ambient temperatures and conditions. It is soluble in common organic solvents like acetone, chloroform and tetrahydrofuran.

H-NM R (400 MHz, (CD ₃ ) ₂ CO): d = 1.44 - 3.50 (br ^a , 18H, 2XBI ₀ H ₉ ), 3.80 (br, s, 4H, 4x0^), 4.17 (s,

2H, C ⁴ H ₂ ), 11.28 (br, s, 1H, C ¹ ΌOH) ppm.

“B^HJ-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -18.2 (s, 2B), -16.9 (s, 2B), -13.9 (s, 4B), -12.7 (s, 4B), -10.4 (s, 2B), -5.9 (s, 4B), -3.8 (s, 2B, 2xBS) ppm. ⁿ B-NM R (128 M Hz, (CD ₃ ) ₂ CO): d - -17.6 (br ^a , 4B), -13.3 (br ^a , 8B), -10.4 (d, BH = 150 Hz, 2B), -5.9 (d, ^BH = 162 Hz, 4B), -3.8 (s, 2B, 2xBS) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, (CD ₃ ) ₂ CO): d = 32.6 (s, C ⁴ H ₂ ), 56.1 (br, s, 4x0^), 169.7 (s, C _q ³ S), 179.4 (s, C _q ⁵ OOH), 179.6 (s, 2xC _q ² S) ppm.

Mass spectrometry (HR-ESI, positive mode, CH2CI2/CH3CN): calculated for C9H26B20N3O2S3: m/z = 521.31608 ([M+H] ⁺ found: m/z = 521.31583 ([M+H] ⁺

/V ⁶ -[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l _f 3,5-triazin-2-yl]-/\/ ² -(ieri- butoxycarbonyl)-L-lysine

In an evacuated and nitrogen-purged 100 mL round-bottom flask 0.20 g (0.43 mmol, 1.00 eq.) 2- chloro-4,6-bis(dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tri azine and 0.12 g (0.49 mmol, l.14 eq.) /V _a -(ferf-butoxycarbonyl)-L-lysine are placed and suspended in a mixture of 20 mL acetonitrile and 25 mL water. To this mixture 0.07 g (1.75 mmol, 4.07 eq.) of sodium hydroxide are added and stirred for 30 minutes at ambient temperature. Then the mixture is heated to reflux and stirred for 18 hours. The reaction process is monitored via TLC (ethyl acetate/n- hexane, 1:1, v/v). The reaction is stopped by adding 1 M hydrochloric acid until acidic pH. The precipitate, which is formed, is filtered off immediately and is washed with water to neutral pH. After column chromatography of the precipitate (acetone/n-hexane, 1:1, v/v, 2.5% glacial acetic acid) 138 mg (0.20 mmol, 46.5%, R/ = 0.65) of the title compound is isolated as a white solid.

/V ⁶ -[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3, 5-triazin-2-yl]-/V ² -(ferf-butoxycarbonyl)- L-lysine is a white solid which is stable under ambient conditions and temperatures. It is soluble in common organic solvents like acetone, tetrahydrofuran and methanol. It is also soluble in very basic aqueous media, like H20/NaOH and MeOH/H20/NaOH.

^! H-NMR (400 MHz, CD ₃ CN): 5 = 1.40 (s, 9H, C(C ¹⁴ H ₃ )B), 1.50 - 3.30 (br ^a , 18H, 2XBI ₀ H ₉ ), 1.59 (br, m, 4H, 2XCH ₂ , C ⁶ ' ⁷ H ₂ ), 1.77 (br, m, 2H, CH ₂ , C ⁸ H ₂ ), 3.38 (br, s, 4H, AxC^ ^' H), 3.41 (m, 2H, C ⁵ H ₂ ), 4.04 (m, 1H, C ⁹ H), 5.54 (d, ³ JHH = 7.8 Hz, 1H, N ⁿ H), 6.20 (m, 1H, N ⁴ H), 9.50 (s, 1H, C ¹⁰ OOH) ppm. “B^HJ-NM R (128 M Hz, CD ₃ CN): d = -18.4 (s, 2B), -17.0 (s, 2B), -14.1 (s, 4B), -12.9 (s, 4B), -10.6 (s, 2B), -6.0 (s, 4B), -3.5 (s, 2B, 2xBS) ppm.

^U B-NM R (128 M Hz, CD ₃ CN): d = -18.4 (br ^a , 2B), -17.0 (br, d, ^BH = 192 Hz, 2B), -13.5 (br ^a , 8B), -10.6 (d, BH = 154 Hz, 2B), -6.0 (d, 166 Hz, 4B), -3.5 (s, 2B, 2xBS) ppm.

“C^Hj-NMR (100 M Hz, CD ₃ CN): d = 23.9 (s, C ^{6 or 7} H ₂ ), 28.6 (s, C(C ¹⁴ H ₃ ) ₃ ), 30.2 (s, C ^{6 or 7} H ₂ ), 32.1 (s, C ⁸ H ₂ ), 41.2 (s, C ⁵ H ₂ ), 54.4 (s, C ⁹ H), 55.9 (br, s, 2xC ^{l or l} 'H), 56.0 (br, s, 2xC ^{l or 4} Ή), 79.9 (s, C _q ¹³ (CH ₃ ) ₃ ), 156.7 (s, 2xC _q ² S), 174.5 (s, C _q ³ ), 178.5 (s, C _q ¹² 0), 179.6 (s, C _q ¹⁰ O) ppm.

I R spectroscopy (KBr, v in cm ^-1 ): 3856 (w), 3455 (m), 3258 (m), 3138 (m), 3058 (m), 2980 (m), 2934 (m), 2864 (m), 2603 (s), 1698 (s), 1614 (s), 1569 (m), 1520 (s), 1500 (s), 1452 (m), 1435 (m), 1410 (s), 1369 (s), 1307 (m), 12477 (s), 1218 (m), 1201 (m), 1166 (s), 1117 (m), 1059 (m), 1022 (w), 994 (w), 954 (m), 863 (s), 850 (s), 801 (m), 760 (m), 731 (m), 668 (w), 642 (w), 590 (w), 418 (w).

Mass spectrometry (HR-ESI, negative mode, CHCI ₃ /CH ₃ CN): calculated for C ₁₈ H ₄₂ B ₂₀ N ₅ O ₄ S ₂ : m/z = 673.46669 ([M-H] ) found: m/z - 673.46701 ([M-H] )

Elemental analysis: calculated (%) for C18H43B20N5O4S2 : C = 32.08, 1-1 = 6.43, N = 10.39; found:

C = 31.17, H = 6.35, N = 10.11.

[^e-Bisll^-dicarba-c/oso-dodecaboran-iJ-ylthioJ-l S S-triazin^-yllglycine

In an evacuated and nitrogen-purged 100 mL two-neck round-bottom flask, equipped with a condenser, 0.27 g (0.58 mmol, 1.00 eq.) 2-chloro-4,6-bis(dicarba-c/oso-dodecaboran-9-ylthio)- 1,3,5-triazine and 0.07 g (0.94 mmol, 1.61 eq.) glycine are placed and suspended in 30 mL acetonitrile. Subsequently, 0.13 g (3.25 mmol, 5.59 eq.) sodium hydroxide, dissolved in 20 mL water, is added to the suspension. The reaction mixture is heated to reflux and 20 mL acetonitrile and 15 mL ethyl acetate are added resulting in a clear solution. The reaction process is monitored via TLC (acetone/n-hexane/glacial acetic acid, 1:1:0.05, v/v/v). After one day, the reaction is stopped by addition of 2 M hydrochloric acid until pH < 7 is reached. All organic solvents are removed under reduced pressure and the remaining aqueous phase is extracted four times with 50 mL diethyl ether. The combined organic phases are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n- hexane, 1:1, v/v, 2.5% glacial acetic acid) 176 mg (0.35 mmol, 60.4%, R/ = 0.14) of the title compound is isolated as a slightly yellow solid.

[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tr iazin-2-yl]glycine is a slightly yellow solid and it is stable at ambient temperatures and conditions. It shows a better solubility in common organic solvents as 2-{[4,6-Bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tr iazin-2- yl]thio}acetic acid. The carboxylic acid group shows a higher reactivity towards triflates than the secondary amine group. The nucleophilicity of the secondary amine group is reduced due to the possible mesomeric delocalization of the free electron pair in the triazine ring. So the reaction of this compound with l,2:3,4-Di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6-t riflate leads to (l',2':3',4'-Di-0-isopropylidene-6'-deoxy-a-D-galactopyranos -6'-yl)[4,6-bis(l,7-dicarba- c/oso-dodecaboran-9-ylthio)-l,3,5-triazin-2-yl]glycinate. ^! H-N M R (400 MHz, (CD ₃ ) ₂ CO): d = 1.40 - 3.60 (br ^a , 18H, 2XBI ₀ H ₉ ), 3.71 (br, s, 4H, 4xC ¹ - ¹ 'H), 4.30 (d, ³ 7 _H H = 6.3 Hz, 2H, C ⁵ H ₂ ), 6.94 (t, ³ 7 _H H = 6.0 Hz, 1H, N ⁴ H), 10.8 (br, s, 1H, C ⁶ OOH) ppm.

“B^HJ-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -18.6 (s, 2B), -17.0 (s, 2B), -14.0 (s, 4B), -12.8 (s, 4B), -10.5 (s, 2B), -5.9 (s, 4B), -3.3 (s, 2B, 2xBS) ppm. ⁿ B-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -18.6 (br ^a , 2B), -17.0 (overlapping signals, 2B), -14.0 (br ^a , 4B), -12.8 (br ^a , 4B), -10.5 (d, BH = 151 Hz, 2B), -5.9 (d, BH = 166 Hz, 4B), -3.3 (s, 2B, 2xBS) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, (CD ₃ ) ₂ CO): d = 42.7 (s, C ⁵ H ₂ ), 55.7 (br, s, 2xC ^{l or} ^H), 55.8 (br, s, 2xC ^{l or l} H), 164.7 (s, C _q ³ NH), 171.5 (s, 2xC _q ² S), 179.9 (s, C _q ⁶ 0) ppm.

I R spectroscopy (KBr, v in cm- ¹ ): 3290 (m), 3056 (s), 2927 (m), 2606 (s), 1714 (s), 1562 (s), 1521 (s), 1494 (s), 1415 (s), 1243 (s), 1176 (s), 1064 (m), 991 (m), 950 (m), 850 (s), 801 (m), 757 (w), 730 (m), 668 (w), 624 (w), 450 (w).

Mass spectrometry (HR-ESI, positive mode, CH2CI2/CH3OH): calculated for C9H27B20N4O2S2: m/z - 504.35497 ([M+H] ⁺ ) found: m/z = 504.35463 ([M+H] ⁺ )

Crystallographic data

Empirical formula Cl2H ₃ oB2oCI ₆ N ₄ 02. ₃₃ S2 Formula weight 760.75 Temperature 130(2) K Wavelength 71.073 pm Crystal system Monoclinic Space group Cc

Unit cell dimensions a - 2061.73(7) pm a = 90° b = 4052.0(1) pm b = 99.327(3)° c = 1310.75(3) pm g = 90°

Volume 10.8054(5) nm ³

Z 12 Density (calculated) 1.403 Mg/m ³

Absorption coefficient 0.619 mm ¹ F(000) 4592

Crystal size 0.4 x 0.3 x 0.2 mm ³

Theta range for data collection 1.80 to 30.35°

I ndex ranges -28 < h < 29, -57 < k < 57, -18 < I < 18

Reflections collected 78083

I ndependent reflections 28909 [R(int) = 0.0416]

Completeness to theta = 28.29° 100.0%

Absorption correction Semi-empirical from equivalents

Max. and min. transmission l and 0.917

Refinement method Full-matrix least-squares on F ²

Data / restraints / parameters 28909 / 623 / 1312

Goodness-of-fit on F ² 1.023

Final R indices [l>2sigma(l)] Rl = 0.0803, wR2 = 0.2104

R indices (all data) Rl = 0.1084, wR2 = 0.2354

Racemic twin Twin domain ratio 0.59(8):0.41(8)

Largest diff. peak and hole 0.813 and -1.109 e-A ³

Comments: Structure solution with SHELXT-2014 (dual space method). Anisotropic refinement of all non-hydrogen atoms, except disordered parts of the structure, with SHELXL-2014. All hydrogen atoms are calculated on idealized positions. All solvent molecules (chloroform and acetone) are disordered. For an acceptable interpretation of the electron density map some of the highly disordered chloroform molecules are treated as three- or fourfold disordered. Most likely as a result of the loosely packed solvent molecules, one carbaborane unit (C26, C27, B51 to B60) is found to be disordered as well with a ratio of 0.61(1):0.39(1). The carbon atoms of the carbaborane units couldn't be localised. The molecular formula of the compound can be given as C9H26B20N4O2S2 · 2 CHCI3 · 1/3 acetone. Significant intermolecular OH···N and NH---0 hydrogen donor acceptor bonds are present forming a trimer (shown in Figure 1).

Hydrogen atoms are omitted for clarity.

Figure 1: I ntermolecular OH···N and NH···0 donor-acceptor bonds (view along the a axis).

(l' Z'iB'^'-Di-O-isopropylidene-e'-deoxy-a-D-galactopyranos-e'-y B-bisil y-dicarba-c/oso- dodecaboran-9-ylthio)-l,3,5-triazin-2-yl]glycinate

A 100 mL Schlenk flask is charged with 90 mg (0.18 mmol, 1.00 eq.) [4,6-bis(l,7-dicarba-c/oso- dodecaboran-9-ylthio)-l,3,5-triazin-2-yl]glycine and 0.13 g (0.94 mmol, 5.22 eq.) potassium carbonate, evacuated and nitrogen-purged. Both starting materials are suspended in 30 mL tetrahydrofuran, the mixture is heated to 40 °C and stirred for three hours. Subsequently, 0.15 g (0.38 mmol, 2.11 eq l,2:3,4-di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6-t riflate, dissolved in 20 mL tetrahydrofuran, is added to the mixture. The reaction mixture is stirred for two days at ambient temperature. The reaction is stopped by adding 30 mL water and the aqueous phase is extracted three times with 25 mL diethyl ether. The combined organic phases are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (n-hexane/ethyl acetate, gradient 3:1 to 100% ethyl acetate, v/v) 84 mg (0.11 mmol, 62.6%, R/ = 0.49, n-hexane/ethyl acetate, 1:1, v/v) of the title compound is obtained as a pure white solid.

( ,2':3',4'-Di-0-isopropylidene-6'-deoxy-a-D-galactopyranos-6' -yl)[4,6-bis(l,7-dicarba-c/o50- dodecaboran-9-ylthio)-l,3,5-triazin-2-yl]glycinate is a pure white solid which is stable under ambient conditions and temperatures. It is well soluble in common organic solvents like acetone, dichloromethane and tetrahydrofuran. It crystallizes well from concentrated acetone solutions. It is the constitutional isomer of /V-[4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3,5-tr iazin- 2-yl]-/V-(l',2':3',4'-di-0-isopropylidene-6'-deoxy-a-D-galac topyranos-6'-yl)glycine. The water solubility for the derivative with the unprotected sugar moiety isn't investigated yet, but it is imaginable that the unprotected compound could act as a surfactant, because of the two hydrophobic carbaborane clusters on the one side and the hydrophilic sugar moiety on the other side.

^! H-NM R (400 MHz, (CD ₃ ) ₂ CO): d = 1.316 (s, 3H, C ¹⁴ ' ¹⁴ Ή ₃ ), 1.322 (s, 3H, C ¹⁵ - ¹⁵ H ₃ ), 1.38 (s, 3H, C ¹⁴ ' ¹⁴ 'H ₃ ), 1.47 (s, 3H, C ¹⁵ ' ¹⁵ 'H ₃ ), 1.50 - 3.50 (br ^a , 18H, 2XBI ₀ H ₉ ), 3.69 (br, s, 2H, 2xC ¹ ' ¹ 'H), 3.74 (br, s, 2H, 2xC ¹ ' ¹ 'H), 4.06 (m, 1H, C ⁷ H), 4.19 (m, 2H, C ⁶ H ₂ ), 4.29 (m, 1H, C ⁹ H), 4.33 (m, 2H, C ⁵ H ₂ ), 4.37 (m, 1H, C ¹⁰ H), 4.64 (virtual dd, ³ J _H H = 7.9 Hz, ³ V _H H = 2.5 Hz, 1H, C ⁸ H), 5.47 (d, ³ J _m = 5.0 Hz, 1H, C ¹⁴ H), 7.05 (t, ³ J _H H = 6.6 Hz, 1H, N ⁴ H) ppm.

¹¹ B{ ¹ H}-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -18.5 (s, 2B), -17.0 (s, 2B), -14.1 (s, 4B), -12.8 (s, 4B), -10.4 (s, 2B), -5.9 (s, 4B), -3.4 (s, 2B, 2xBS) ppm. ⁿ B-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -20.4 to -9.2 (br ^a , 14B), -5.9 (d, ^BH = 149 Hz, 4B), -3.4 (s, 2B, 2xBS) ppm.

^C^HJ-NMR (100 M Hz, (CD ₃ ) ₂ CO): d = 24.7, 25.2, 26.3 and 26.4 (s, 4xCH ₃ , C ¹⁴ H ₃ , C ¹⁴ 'H ₃ , C ¹⁵ H ₃ and C ^15' H ₃ ), 42.9 (s, C ⁵ H ₂ ), 55.6 (br, s, 2xC ^{l or l'} H), 55.9 (br, s, 2xC ^{l or l'} H), 64.7 (s, C ⁶ H ₂ ), 66.6 (s, C ⁷ H), 71.3 (s, C ¹⁰ H), 71.5 (s, C ⁸ H), 71.8 (s, C ⁹ H), 97.1 (s, C H), 109.2 (s, C _q ¹³ ), 109.9 (s, C _q ¹² ), 164.7 (s, C _q ³ ), 170.7 (s, 2xC _q ² ), 179.8 (s, C _q , C ¹⁶ 0) ppm.

Mass spectrometry (HR-ESI, positive mode, (CH ₃ ) ₂ CO): calculated for C ₂ IH ₄ 5B ₂ ON407S ₂ : m/z = 746.47131 ([M+H] ⁺ ) found: m/z - 746.47144 ([M+H] ⁺ ) calculated for C _2i H44B ₂ oN4NaiOS ₂ : m/z = 768.45326 ([M+Na] ⁺ ) found m/z = 768.45314 ([M+Na] ⁺ )

Crystallographic data Empirical formula C ₂₂ .5OH47B ₂ ON407.5OS ₂ Formula weight 773.96 Temperature 130(2) K Wavelength 71.073 pm Crystal system Monoclinic Space group P2i

Unit cell dimensions a = 1122.40(3) pm a = 90'

b = 3037.83(7) pm b = 106.902(3)° c = 1243.49(4) pm g = 90°

Volume 4.0567(2) nm ³

Z 4

Density (calculated) 1.267 Mg/m ³

Absorption coefficient 0.178 mm ¹

F(000) 1608

Crystal size 0.4 x 0.2 x 0.1 mm ³

Theta range for data collection 2.01 to 28.31°

I ndex ranges -14 < h < 14, -40 < k < 39,—15 < I < 14

Reflections collected 36542

I ndependent reflections 17888 [R(int) = 0.0395]

Completeness to theta = 26.38° 100.0%

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 1 and 0.99777

Refinement method Full-matrix least-squares on F ²

Data / restraints / parameters 17888 / 1 / 1275

Goodness-of-fit on F ² 0.987

Final R indices [l>2sigma(l)] Rl = 0.0452, wR2 = 0.0732

R indices (all data) Rl = 0.0682, wR2 = 0.0802

Absolute structure parameter 0.04(3)

Largest diff. peak and hole 0.215 and -0.208 e-A ³

Comments: Structure solution with SHELXT-2014 (dual-space method). Anisotropic refinement of all non-hydrogen atoms with SHELXL-2014. Excluding methyl hydrogen atoms, all H atoms were located on difference Fourier maps calculated at the final stage of the structure refinement. Carbaborane C atoms were localised from a bond length and isotropic displacement parameter analysis. Dimers are formed through intermolecular NH···N donor-acceptor bonds.

Hydrogen atoms are omitted for clarity.

ferf-Butyl-/V-{2-[(4,6-dichloro-l,3,5-triazin-2-yl)-2-(l ^, ,2':3 ^, ,4 ^, -di-0-isopropylidene-6 ^, -deoxy-a-

D-galactopyranos-6'-yl)-amino]ethyl}carbamate

18 O = B ato m

18

I n an evacuated and nitrogen-purged 100 mL Schlenk flask, charged with 1.99 g (5.07 mmol, 1.00 eq.) 1,2:3, 4-di-0-isopropylidene-6-deoxy-a-D-galactopyranosyl-6-triflat e (14) dissolved in 50 mL acetonitrile, 0.90 g (0.89 mL, 5.64 mmol, 1.11 eq.) tert-Butyl A/-(2-aminoethyl)carbamate were added. Subsequently 1.05 mL (0.80 g, 6.17 mmol, 1.22 eq.) diisopropylethylamine are slowly added at room temperature to the mixture and the mixture is allowed to stir for two days at 40 °C. A solution of 1.56 g (8.46 mmol, 1.67 eq.) cyanuric chloride and 1.05 mL (0.80 g, 6.17 mmol, 1.22 eq.) diisopropylamine in 20 mL acetonitrile is slowly added at 0 °C and the reaction mixture is stirred for two days at 35 °C. The reaction is stopped by adding 30 mL of a saturated sodium chloride solution; the resulting layers are separated. The aqueous phase is extracted four times with 20 mL ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n-hexane, 1:3, v/v) 1.90 g (3.46 mmol, 68.2%, R/ = 0.31) of the title compound is obtained as a colorless solid. terf-Butyl-A/-{2-[(4,6-dichloro-l,3,5-triazin-2-yl)-2-(l',2' :3',4'-di-0-isopropylidene-6'-deoxy-a-D- galactopyranos-6'-yl)-amino]ethyl}carbamate is a under ambient conditions stable colorless solid. When the solvent is removed under reduced pressure it forms foam-like structures. It is soluble in all common organic solvents like acetone, chloroform, tetrahydrofuran and acetonitrile.

^! H-NM R (400 MHz, (CDB) ₂ CO): d = 1.29 (s, 3 H, C ¹⁷ ' ¹⁷ 'H ₃ ), 1.35 (s, 3 H, C ¹⁸ ' ¹⁸ 'H ₃ ), 1.38 (s, 12 H, C ^{17 17} 'H ₃ and C^Hsh), 1.43 (s, 3 H, C ¹⁸ ' ¹⁸ 'H ₃ ), 3.39 (m, 2 H, C ⁵ H ₂ ), 3.76 (m, br, 3 H, C ⁶ HH and C ⁹ HH and C ⁹ HH), 3.92 (m, 1 H, C ⁶ HH), 4.25 (m, 1 H, C ¹⁰ H), 4.28 (m, 1 H, C ⁿ H), 4.36 (dd, ³ 7 _H H = 5.1 Hz, ³ 7HH = 2.5 Hz, 1 H, C ¹³ H), 4.65 (dd, ³ J _H H = 7.9 Hz, ³ 7 _H H = 2.4 Hz, 1 H, C ¹² H), 5.48 (d, ³ 7 _H H = 5.0 Hz, 1 H C ¹⁴ H), 6.12 (t, ³ 7HH = 6.3 Hz, 1 H, N ⁴ H) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, (CD ₃ ) ₂ CO): d = 24.7, 25.2, 26.2 and 26.4 (s, 4xCH ₃ , C ¹ Ή ₃ , C ^17' H ₃ , C ¹⁸ H ₃ and C ¹⁸ 'H ₃ ), 28.6 (s, C(C ¹ H ₃ ) ₃ ), 38.5 (s, C ⁵ H ₂ ), 50.1 (s, C ⁶ H ₂ ), 50.3 (s, C ⁹ H ₂ ), 65.7 (s, C ¹⁰ H), 71.3 (s, C ¹³ H), 71.7 (s, C ¹² H), 72.0 (s, C H), 78.8 (s, C _q ² (CH ₃ ) ₃ ), 97.3 (s, C ¹⁴ H), 109.3 (s, C _q ¹⁵ ), 110.0 (s, Cq ¹⁶ ), 156.7 (s, Cq ³ ), 166.3 (s, Cq ⁸ ), 170.27 and 170.32 (s, 2xC _q ⁷ ) ppm.

Mass spectrometry (HR-ESI, positive mode, (CH3) ₂ CO):

Calculated for C22H33O7N5CI2: m/z = 572,1655 ([M+Na] ⁺ ) m/z = 1123,3383 ([2M+Na] ⁺ ) m/z = 550,1836 ([M+H] ⁺ )

Found: m/z = 572,1651([M+Na] ⁺ , 100%) m/z = 1123,3383 ([2M+Na] ⁺ , 28%) m/z = 550,51833 ([M+H] ⁺ , 20%)

ieri-Butyl-/V-{2-[(4,6-bis(l,7-dicarba-c/oso-dodecaboran- 9-ylthio)-l,3,5-triazin-2-yl)-2-

(r,2':3\4'-di-0-isopropylidene-6'-deoxy-a-D-galactopyrano s-6'-yl)-amino]ethyl}carbamate

A 250 mL two-neck round-bottom flask, equipped with a condenser, is charged with 0.98 g (5.56 mmol, 3.04 eq.) 9-(mercapto)-l,7-dicarba-c/oso-dodecaborane(12) (4) and 1.16 g (8.39 mmol, 4.58 eq.) potassium carbonate, evacuated and nitrogen-purged. The starting materials are suspended in 80 mL acetonitrile. A separate Schlenk flask is charged with 1.01 g (1.83 mmol, 1.00 eq.) fert-Butyl-A/-{2-[(4,6-dichloro-l,3,5-triazin-2-yl)-2-(l',2' :3',4'-di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)-amino]ethy l}carbamate, evacuated, nitrogen-purged and then dissolved in 30 mL acetonitrile. The solution containing the carbamate is added dropwise to the reaction mixture and the mixture is then stirred under reflux for two days. The reaction is stopped by adding 25 mL of a saturated aqueous sodium chloride solution. The resulting layers are separated and the aqueous phase is extracted three times with 30 mL ethyl acetate. The combined organic layers are dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. After column chromatography (ethyl acetate/n- hexane, 1:2, v/v) 1.50 g (1.80 mmol, 98.6%, R/ = 0.21) of the title compound is obtained as a white solid. tert-Butyl-/V-{2-[(4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-y lthio)-l,3,5-triazin-2-yl)-2-

(l',2':3',4'-di-0-isopropylidene-6'-deoxy-a-D-galactopyra nos-6'-yl)-amino]ethyl}carbamate is also stable under ambient conditions. It forms also these foam-like colorless structures when it's dried in vacuum. I n comparison to the glycine derivatives it seems than these type of compounds show a higher solubility in common organic solvents like acetone, acetonitrile, chloroform and tetrahydrofuran.

^! H-NM R (400 MHz, CDCI3): d = 1.28 (s, 3 H, C ¹⁸ ' ^18' H ₃ ), 1.35 (s, 3 H, C ^{19 19'} H ₃ ), 1.41 (s, 12 H,

C ^{18 18} 'H ₃ and C(C ⁹ H ₃ ) ₃ ), 1.48 (s, 3 H, C ¹⁹ ' ¹⁹ 'H ₃ ), 1.55 - 3.55 (br ³ , 18 H, 2XBI ₀ H ₉ ), 2.98 (br, s, 4 H, 4xC ¹ H), 3.40 (m, 2 H, C ⁵ H ₂ ), 3.45 (m, 1 H, C ¹⁰ HH), 3.64 (dt, I/HH = 13.3 Hz, I/HH = 5.6 Hz, 1 H, C ⁴ HH), 4.03 (dd, ³ J _H H = 14.4 Hz, 1/ _H H = 3.2 Hz, 1 H, C ¹⁰ HH), 4.14 (m, 1 H, C ⁴ HH), 4.28 (m, 3 H, C H, C ¹² H and C ¹⁴ H), 4.59 (dd, I/HH = 7.9 Hz, I/HH = 2.3 Hz, 1 H, C ¹³ H), 5.33 (m, 1 H, N ⁶ H), 5.50 (d,

I/HH = 4.9 Hz, 1 H, C ¹⁵ H) ppm.

¹¹ B{ ¹ H}-NM R (128 M Hz, CDCI ₃ ): d = -18.8 (s, 2B), -17.3 (s, 2B), -14.0 (s, 4B), -12.9 (s, 4B), -10.1 (s, 2B), -5.6 (s, 4B), -3.1 (s, 2B, 2xBS) ppm.

^U B-NM R (128 M Hz, CDCI ₃ ): d = -20.9 to -11.4 (br ^a , 12B), -10.1 (d, BH = 151 Hz, 2B), -5.6 (d, BH = 166 Hz, 4B), -3.1 (s, 2B, 2xBS) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, CDCI ₃ ) : d = 24.4, 25.1, 26.06 and 26.08 (s, 4xCH ₃ , C ¹⁸ H ₃ , C ¹⁸ 'H ₃ , C ¹⁹ H ₃ and C ^19' H ₃ ), 28.4 (s, C(C ⁹ H ₃ ) ₃ ), 39.7 (s, C ⁵ H ₂ ), , 48.7 (s, C ⁴ H ₂ ), 49.0 (s, C ¹⁰ H ₂ ), 53.9 and 54.0 (s, 4xCH, 2xC ¹ H and 2xC ¹ H), 66.2 (s, C ⁿ H), 70.5 (s, C ¹⁴ H); 70.9 (s, C ¹³ H), 71.7 (s, C ¹² H), 78.8 (s, C _q ⁸ ), 96.3 (s, C ¹⁵ H), 109.0 (s, C _q ¹⁶ ), 109.3 (s, C _q ¹⁷ ), 156.1 (s, C _q ⁷ ), 163.3 (s, C _q ³ ), 178.1 (s, C _q ² ) ppm.

Mass spectrometry (HR-ESI, positive mode, (CH ₃ ) ₂ CO): Calculated for C26H55B20O7N5S2: m/z = 831,55915 ([M+H] ⁺ )

Found: m/z = 831,5612([M+H] ⁺ , 100%)

N^i^S-bisil^-dicarba-c/oso-dodecaboran-S-ylthioJ-l B S-triazin-Z-ylJ-N^ilil' Z'iS'^'-di-O- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)ethane-l, 2-diamine

A Schlenk flask is charged with 353 mg (425 mitioI, 1.00 eq.) fe/t-Butyl-/V-{2-[(4,6-bis(l,7-dicarba- c/oso-dodecaboran-9-ylthio)-l,3,5-triazin-2-yl)-2-(l',2':3', 4'-di-0-isopropylidene-6'-deoxy-a-D- galactopyranos-6'-yl)-amino]ethyl}carbamate, evacuated and nitrogen-purged, and 10 mL of dichloromethane were added. Subsequently, 1.65 mL (2.44 g, 21.4 mmol, 50.4 eq.) trifluoroacetic acid is added and the mixture is stirred for four hours at room temperature. The reaction is stopped by removing the solvent under reduced pressure. The raw product was directly purified by column chromatography (ethyl acetate/n-hexane, 2:1 (v/v) to ethyl acetate, 100%) and 283 mg (388 pmol, 91.2%, R/= 0.05(100% ethyl acetate)) of the title compound is obtained as an off-white solid.

N ¹ -(4,6-bis(l,7-dicarba-c/oso-dodecaboran-9-ylthio)-l,3, 5-triazin-2-yl)-N ¹ -(((l',2':3',4'-di-0- isopropylidene-6'-deoxy-a-D-galactopyranos-6'-yl)ethane-l, 2-diamine is an off-white solid, which also forms foam-like structures when the solvent is evaporated under reduced pressure. Comparing the R _f -value in pure ethyl acetate with the glycine derivative it seems that the diamine derivative is much more polar and also it seems that this compound is more soluble in common organic solvents like chloroform, acetone, acetonitrile and tetrahydrofuran.

^! H-N M R (400 M HZ, (CD ₃ ) ₂ CO): 6 = 1.28 (s, 3 H, C ¹⁵ ' ^15' H ₃ ), 1.34 (s, 3 H, C ¹⁶ ' ^16' H ₃ ), 1.35 (s, 3 H, C ^{15 15} H ₃ ), 1.44 (s, 3 H, C ^{16 16'} H ₃ ), 1.53 - 3.40 (br ^a , 18 H, 2XBI ₀ H ₉ ), 3.56 (dd, ³ V _H H = 15.4 HZ, ³ 7HH = 10.2 Hz, 1 H, C ⁷ HH), 3.80 and 3.82 (s, 4xCH, 2xC ³ H and 2xC ¹ 'H), 3.95 - 4.25 (br, m, 6 H, 2xC ⁴ HH, 2xC ⁵ HH, C ⁷ HH and C ⁸ H), 4.35 (m, 2 H, C ⁹ H and C H), 4.62 (dd, ³ 7HH = 7.9 Hz, ³ VHH = 2.5 Hz, C ¹⁰ H), 5.51 (d, ³ J _H H = 5.0 Hz, C ¹² H) ppm.

“B^HJ-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -19.6 (s, 2B), -17.9 (s, 2B), -14.9 (s, 4B), -13.7 (s, 4B), - 11.3 (s, 2B), -6.9 (S, 4B), -4.4 (s, 2B, 2xBS) ppm. ⁿ B-NM R (128 M Hz, (CD ₃ ) ₂ CO): d = -21.3 to -12.3 (br ^a , 12B), -11.3 (d, ^BH = 149 Hz, 2B), -6.9 (d, BH = 165 Hz, 4B), -4.4 (s, 2B, 2xBS) ppm.

¹³ C{ ¹ H}-NM R (100 M Hz, (CD ₃ ) ₂ CO) : d = 24.7, 25.2, 26.3 and 26.4 (s, 4xCH ₃ , C ¹⁵ H ₃ , C ¹⁵ 'H ₃ , C ¹⁶ H ₃ and C ^16' H ₃ ), 45.8 (s, C ⁵ H ₂ ), 47.9 (s, C ⁴ H ₂ ), 49.9 (s, C ⁷ H ₂ ), 56.0 and 56.1 (s, 2xC ³ H and 2xC ^1' H), 67.2 (s, C ⁸ H), 71.3 (s, C H), 71.8 (s, C ¹⁰ H), 72.4 (s, C ⁹ H), 97.3 (s, C ¹² H), 109.3 (s, C _q ¹³ ), 110.0 (s, C _q ¹⁴ ), 163.9 (s, Cq ³ ), 179.0 and 179.5 (s, 2xC _q ² ) ppm.

Mass spectrometry (HR-ESI, positive mode, (Ch CO):

Calculated for C21H47B20O5N5S2: m/z = 731,50671 ([M+H] ⁺ ) m/z = 774,56036 ([M+C ₂ H ₇ N] ⁺ ) Found: m/z = 731,5082([M+H] ⁺ , 54%) m/z = 774,5620 ([M+C ₂ H ₇ N] ⁺ , 100%)