Journal of the American Chemical Society 2004-04-07

A versatile chemo-enzymatic route to enantiomerically pure beta-branched alpha-amino acids.

Geoffrey J Roff, Richard C Lloyd, Nicholas J Turner

Index: J. Am. Chem. Soc. 126 , 4098-4099, (2004)

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Abstract

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.