A divergent approach to the preparation of cysteine and serine analogs

Douglas S. Masterson, University of Southern Mississippi
Kinkini Roy, University of Southern Mississippi
Dale A. Rosado, University of Southern Mississippi
Marilyn Fouche, University of Southern Mississippi


Malonate diesters containing a prochiral quaternary carbon have been successfully transformed into analogs of cysteine and serine. The chiral half-esters are obtained in good yield, and enantioselectivity by selective hydrolysis using Pig-Liver Esterase (PLE) as the catalyst. The resulting half-ester intermediates are transformed into alpha(2,2-), beta(2.2-), and beta(3.3)-analogs of cysteine and serine. The methodology described here allows for the preparation of both enantiomers of the amino-acid analogs by selective manipulation of the ester and acid functional I ties. This divergent strategy allows a common synthetic strategy to be used to prepare a variety of unnatural amino-acid classes from a common intermediate which should prove useful in the design of novel peptide libraries. Copyright (C) 2008 European Peptide Society and John Wiley & Sons. Ltd.