Chemoenzymatic Synthesis of α-Substituted Serines via Enantiodivergent Transformation

A series of (R)-N-Cbz-2-alkyl-2-amino-3-hydroxypropyl acetates was prepared by enzymatic acetylation of N-Cbz-2-alkyl-2-aminopropane-1,3-diols with immobilized lipoprotein lipase from Pseudomonas sp. in up to 98% enantiomeric excess (ee).Enantiodivergent oxidation of (R)-N-Cbz-2-alkyl-2-amino-3-hydroxypropyl acetates readily furnished (R)-and (S)--substituted serines ( -benzylserines and -methylserines).Enzymatic hydrolysis of diethyl N-Cbz-2amino-2-methylmalonate catalyzed by porcine liver esterase afforded (R)-N-Cbz-2-amino-3-ethoxy-2-methyl-3oxopropanoic acid in 97% ee.(R)-N-Cbz-2-amino-3-ethoxy-2-methyl-3-oxopropanoic acid was also transformed to both enantiomers