Asymmetric catalysis of the Strecker amino acid synthesis by a cyclic dipeptide

Summary A novel cyclic dipeptide —cyclo(S)-His-(S)-NorArg] — has been prepared which catalyzes an enantioselective version of the Strecker amino acid synthesis. The catalyst, when present in 2 mol % quantity in methanol solution, catalyzes the addition of hydrogen cyanide toN-alkylimines to afford-amino nitriles in high yield and high enantiomeric excess. Furthermore, acid hydrolysis ofN-benzhydryl--amino nitriles afforded the corresponding-amino acids directly. This methodology affords a variety of arylglycines in exceptionally high enantiomeric excess, but aliphatic amino acids were obtained with low enantioselectivity. Current efforts are underway to expand the scope of this reaction, as well as to elucidate the mechanism of catalysis and the roles played by substrate and catalyst in determining the stereochemical outcome of the reaction.A preliminary communication on this work has recently appeared in: Iyer MS, Gigstad KM, Namdev ND, Lipton MA (1996) J Am Chem Soc 118: 4910–4911.