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

An efficient methylene insertion reaction to construct an S-CH2-S bridge be tween two cysteine residues occurred when the thiol-protecting dimethylphos phinothioyl (Mpt) group of Z-Cys(Mpt)-OMe was removed with tetrabutylammoni um fluoride hydrate in CH2Cl2. The thiol-free form gave similar results, al beit the yields were somewhat lower. In both cases, the best yields were ob tained using 2 molar amounts of the reagent. Higher amounts of the reagent reduced the yield because of dehydroalanine formation. In the case of penic illamine, 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. T he reaction was successfully used in a synthesis of a cyclic enkephalin ana log with the S-CH2-S bridge.