Synthesis of beta-heterosubstituted alpha,alpha-disubstituted alpha-amino acid derivatives via enzyme-catalyzed desymmetrization

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alpha,alpha-disubstituted beta-amino acids having heteroatoms (oxygen, sulfur or nitrogen) at beta-position are versatile intermediates for synthesis of drugs. In this project, we set up our goal to establish novel and efficient methods to assemble them via lipase-catalyzed enantioselective acetylation (desymmetrization) of symmetric 1,3-propanediol to construct the asymmetric quaternary carbon center.Ranirestat, an aldose reductase inhibitor for treatment of diabetic complications, has beta-heterosubstituted alpha,alpha-disubstituted alpha-amino acid moiety, and is enantioselectively synthesized (>99% enantiomeric excess). A practical and enantioselective method to access N-carbobenzoxy (S)-alpha-methylserine is also established.