A versatile chemo-enzymatic route to enantiomerically pure beta-branched alpha-amino acids.
A series of diastereoisomers of beta-methyl-beta-phenylalanine analogues 1a-f have been prepared in enantiomerically pure form using a combination of chemo- and biocatalysis. Starting from l-threonine methyl ester 2, a range of beta,beta-disubstituted didehydroamino acids were obtained as their (Z)-isomers 6a-f. Asymmetric hydrogenation of these alkenes, using either the [Rh(R,R)-Et-DuPhos(COD)]BF4 or [Rh(S,S)-Et-DuPhos(COD)]BF4 catalyst, followed by hydrolysis yielded two of the four possible sets of diastereoisomers of the beta-branched amino acid. Subsequent stereoinversion, using a stereoselective amino acid oxidase in combination with a nonselective reducing agent, furnished the remaining two sets of diastereomers.
Roff
Geoffrey J
GJ
School of Chemistry, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh, EH9 3JJ, U.K.
Lloyd
Richard C
RC
Turner
Nicholas J
NJ