SYNTHESIS OF 4-SULFUR-SUBSTITUTED (2S,3R)-3-PHENYLSERINES BY ENZYMATIC RESOLUTION - ENANTIOPURE PRECURSORS FOR THIAMPHENICOL AND FLORFENICOL

Enantiomerically pure 4-methylthio- and 4-methylsulfonyl-substituted ( 2S,3R)-3-phenylserines are prepared by enzymatic resolution of the cor responding racemic three almides using the amidase from Ochrobactrum a nthropi NCIMB 40321. The unwanted (2R,3S) enantiomers of the amides ar e separated from the enantiopure amino acids and easily racemized afte r Schiff base formation with the corresponding 4-(methylthio)- and 4-( methylsulfonyl)benzaldehyde. The racemization can be combined with the preparation of the racemic amides by aldol reaction under crystalliza tion conditions to yield only the threo isomers. Enantiopure (2S, 3R)- 3-[4-(methylthio)phenyl]serine and (2S,3R)-3-[4-(methylsulfonyl)phenyl are thus obtained in 78% and 62% overall yields starting from the cor responding substituted benzaldehydes, (2S,3R)-3-[4-(methylsulfonyl)phe nyl]serine is reduced to )-2-amino-1-[4-(methylthio)phenyl]propane-1,3 -diol with NaBH4/H2SO4 and can be used for the synthesis of thiampheni col and florfenicol.