Synthesis of 3-Amino-1-carboxy-o-carborane and an Improved, General Method for the Synthesis of All Three C-Amino-C-carboxycarboranes

Abstract

Amino acids of the polyhedral carboranes have potential applications in boron neutron capture therapy and in other areas of bioorganic chemistry, but simple, general methods for their synthesis are nonexistent. A general method for synthesis of C-amino-C-carboxy derivatives of o-, m-, and p-carborane is reported, starting from their respective monoacids and proceeding through nucleophilic attack by an alcohol on the intermediate C-isocyanates. Deprotection of the resulting carbamates provides a simple method for access to the C-amines. Alternatively, the C-isocyanates can be isolated for further reactions. Carbonylation of the carbamates at the remaining carboranyl CH results in high-yield production of the carbamate-protected amino acid. Another related method for the high-yield preparation of the isomeric 3-amino-1-carboxy-o-carborane is also described which makes available for the first time all four reasonably accessible members of the series.

Reduction of hydroxy-functionalised carbaboranyl carboxylic acids and ketones by organolithium reagents

“…The tertbutyloxycarbonyl (Boc) group was chosen as a rather small group which is stable under alkaline conditions, also in the presence of n-BuLi, and can be directly introduced during the synthesis of the carbaboranyl amine from an intermediate isocyanate. 12 Carboxylation of the Boc-protected carbaboranyl amine has already been reported. 12 However, reaction with n-BuLi did not yield the tertiary alcohol but only led to cleavage of the exo-polyhedral C-C bond (reaction V, Table 1).…”

“…1-Hydroxy-1,2-dicarba-closo-dodecaborane (12). The compound was synthesised according to the literature.…”

“…Unconsumed starting material and 1-acetoxy-1,2-dicarba-closododecaborane (12) were in agreement with the calculated ones. 1-Hydroxy-2-acetyl-1,2-dicarba-closo-dodecaborane (12). Deprotection of 1-acetoxy-2-acetyl-1,2-dicarba-closo-dodecaborane (12) was performed under acidic conditions (not under nitrogen atmosphere).…”

“…Unconsumed starting material was separated from the product by column chromatography (n-hexane-ethyl acetate 10 : 1 Reduction of 1-hydroxy-2-acetyl-1,2-dicarba-closo-dodecaborane (12). The reaction was carried out as described for the reduction of 1-acetyl-1,2-dicarba-closo-dodecaborane (12 1-[(tert-Butyloxycarbonyl)amino]-1,2-dicarba-closo-dodecaborane (12). The compound was synthesised according to the literature.…”

Synthesis, characterization and radiolabeling of carborane-functionalized tetrazines for use in inverse electron demand Diels–Alder ligation reactions

“…Carborane-functionalized tetrazines were synthesized starting with para-and ortho-clusters bearing carboxylic acids, where 1,12-dicarba-closo-dodecaborane-1-carboxylic acid (1), and 1,2-dicarba-closo-dodecaborane-1-carboxylic acid (5) were prepared according to literature procedures [68]. Attempts to couple 1 and 5 to the commercially available Tz 3, with standard peptide reagents including PyBOP [69] failed to produce the desired products.…”