Disulfide Bond Construction as a Convenient Route to closo -Carboranyl Derivatives of Cysteine and Glutathione

A method for the preparation of asymmetric disulfides containing 1,2-dicarba-closo-dodecaborane and (R)-cysteine residues was developed. The approach to creating the S–S bond is based on the interaction of thiols with thiosulfonates and makes possible the targeted synthesis of unsymmetrical disulfides based on natural molecules, starting from readily available reagents that are stable to the action of moisture and atmospheric oxygen. We demonstrated that cysteine and glutathione conjugates containing a (closo-carboranyl)acetic acid moiety attached via a cysteamine residue and a disulfide bridge can be obtained using either a strategy based on the use of acid-labile protecting groups or an approach that involves creating a disulfide bond in an aqueous medium without using protecting groups. The proposed approach opens up broad prospects for chemoselective functionalization of compounds containing thiol groups, which can be used in the design of new agents for boron neutron capture therapy and related modalities.