Design and Synthesis of Carboranyl Peptides as Carriers of 1,2-Dicarbadodecarborane Clusters

The carboranyl amino acid 5-(2-methyl-1,2-dicarba-closo-dodecarborane (12)-1-yl)-2-aminopentanoic acid protected as the Boc derivative 1 has been used for the synthesis of peptides 2a-10 differing in chain length and boron content. Alternating the bulky hydrophobic Boc-carboranyl amino acid 1 with hydrophilic residues like serine led to a remarkable improvement in solubility of the peptides without the need to convert the closo-carborane cages into the anionic nido-forms. Conventional procedures of solution peptide synthesis were used, employing the mixed-anhydride method for the condensation steps, the tert-butoxycarbonyl group for intermediate N^α-protection and benzyl-type groups for side-chain protection, resulting in good overall yield. Both acidolytic and hydrogenolytic deprotection steps did not harm the closo-carborane cage. Hydrogenolysis reduced the yields of 5 and 10 drastically due to strong adsorption onto the palladium catalyst.