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

Abstract

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 affordα-amino nitriles in high yield and high enantiomeric excess. Furthermore, acid hydrolysis ofN-benzhydryl-α-amino nitriles afforded the correspondingα-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.

Catalytic asymmetric processes

“…Using 2 mol% of the cyclic dipeptide 25, this transformation may be achieved in up to 99% ee and 97% yield (Scheme 21). 132,133 Titanium() complexes of chiral salen ligands also work well in this application 134 (87% ee).…”

The Upside of Downsizing: Asymmetric Trifunctional Organocatalysts as Small Enzyme Mimics for Cooperative Enhancement of Both Rate and Enantioselectivity With Regulation

“…The Lipton, Jacobsen, and Corey groups reported hydrocyanation of imines catalyzed by a cyclic dipeptide, a thiourea, and a guanidine, respectively (eqs. 10, 11, and 12) with enantioselectivity up to 99% at 2–10 mol% loading . Concurrently, the Miller group reported an N ‐alkylimidazole tripeptide for catalyzing kinetic resolution of alcohols at 84% ee (eq.…”

Journey Heading towards Enantioselective Synthesis Assisted by Organocatalysis

“…The organocatalytic asymmetric ring opening of epoxides has gained great interest in last few years . The development of peptides as catalysts for asymmetric reactions, such as enantioselective Michael,– Strecker,– epoxidation,– acylation reactions– and aldol,– has been reported. Further, Nature uses epoxide hydrolase for the ring opening of epoxide where the phenolic OH group of two tyrosine residues (Tyr152 and Tyr215) activate the epoxide ring towards nucleophilic attack.…”