BIOCONVERSION PROCESS FOR THE SYNTHESIS OF (S)-3-HYDROXY-3-PHENYLPROPIONATE BY CATALYTIC ANTIBODY
Ou Zhimin and Yang Gensheng
Pharmaceuticals College, Zhejiang University of Technology, Hang Zhou, Zhejiang, 310014, P.R. China.
Abstract:
(S)-3-hydroxy-3-phenylpropionate was an important intermediate in the synthesis of (S)-fluoxetine. (S)-fluoxetine was used in anti-depressant drug. A kind of monoclonal antibody NB3 was selected to be catalyst for synthesis of (S)-3-hydroxy-3-phenylpropionate by asymmetric reduction of 3-oxo-3-phenylpropionic acid ethyl ester. The hapten was oxidation state 5-(N-methyl) phenylamino pentanoic acid. The whole antigen was prepared by crosslinking hapten with BSA. The monoclonal antibody NB3 was prepared by hybridoma technology. The molecular weight of catalytic antibody NB3 was 187 KDa. The optimum temperature and pH for reduction was 30 0C and 7.5. Conversion increased with the extension of reduction time. Conversion decreased with addition more amount of substrate and less amount of monoclonal antibody NB3. Conversion reached 99.2% and enantiometric excess of (S)-3-hydroxy-3-phenylpropionate was above 99.0% when substrate concentration was 2 g/L.
Keywords:Catalytic antibody, asymmetric reduction and (S)-3-hydroxy-3-phenylpropionate.
