Dynamic kinetic resolution : synthesis of optically active α-amino acid derivatives

The dynamic kinetic resolution of 2-phenyl-4-subsittuted-5(4H)-oxazolones 89a-g has been investigated as a method for the synthesis of optically active α-amino acid derivatives. The effects of lipase, [either Novozyme (Candida antarctica lipase B), or Lipozyme (Rhizomucor miehei lipase)], solvent, nucleophile, and the addition of external triethylamine to the reaction is described. When R¹ = Ph, an 88% yield and 98% enantiomeric excess (e.e.) of α-amino acid ester 96a was obtained with Novozyme^® in acetonitrile as solvent. The synthesis of novel 5(4H)-oxazolones 129a-e, which are identified as key intermediates in the synthesis of a series of matrix metalloproteinase inhibitors 94, is described. Application of the lipase catalysed dynamic kinetic resolution conditions to 129a-e, afforded high yields (96%) and diastereomeric excesses (d.e.'s), (86%) of the resulting pseudodipeptides (2R,2'S)-127a-e and 130-132, by careful selection of the reaction conditions.(Figs. 1382A and 1382B).