A new efficient method for S-CH2-S bond formation and its application to a djenkolic acid-containing cyclic enkephalin analog

Article abstract of DOI:10.1246/bcsj.72.829

An efficient methylene insertion reaction to construct an S-CH₂-S bridge between two cysteine residues occurred when the thiol-protecting dimethylphosphinothioyl (Mpt) group of Z-Cys(Mpt)-OMe was removed with tetrabutylammonium fluoride hydrate in CH₂Cl₂. The thiol-free form gave similar results, albeit the yields were somewhat lower. In both cases, the best yields were obtained using 2 molar amounts of the reagent. Higher amounts of the reagent reduced the yield because of dehydroalanine formation. In the case of penicillamine, the thiol-free form was better in reactivity than the S-Mpt form, which required double the amount of the reagent to give the same yield. The reaction was successfully used in a synthesis of a cyclic enkephalin analog with the S-CH₂-S bridge.