A divergent approach to the preparation of cysteine and serine analogs.
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 alpha2, 2-, beta2, 2-, and beta3, 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 functionalities. 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.
Masterson
Douglas S
DS
The University of Southern Mississippi, Department of Chemistry and Biochemistry, Hattiesburg, MS 39406, USA. Douglas.Masterson@usm.edu
Roy
Kinkini
K
Rosado
Dale A
DA
Fouche
Marilyn
M
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001671:Biochemistry / Q000379:methods; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D003545:Cysteine / Q000737:chemistry*; D004950:Esterases / Q000737:chemistry; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D012694:Serine / Q000737:chemistry*; D013237:Stereoisomerism; D013552:Swine
D000596:Amino Acids; D010455:Peptides; D012694:Serine; D002244:Carbon; D004950:Esterases; D003545:Cysteine