Chemo-enzymatic synthesis of (S)-α-cyano-3-phenoxybenzyl alcohol
1998; Elsevier BV; Volume: 9; Issue: 1 Linguagem: Inglês
10.1016/s0957-4166(97)00608-3
ISSN1362-511X
Autores Tópico(s)Microbial Metabolic Engineering and Bioproduction
ResumoA chemo-enzymatic process for the preparation of (S)-α-cyano-3-phenoxybenzyl alcohol (S-CPBA), an important intermediate in the synthesis of many pyrethroids, was developed. The process consists of four stages, including lipase-mediated resolution. The first stage, the synthesis of racemic α-cyano-3-phenoxybenzyl acetate (CPBAc) from m-phenoxybenzaldehyde (m-PBA) and sodium cyanide in the presence of a phase transfer catalyst, resulted in a 75% yield with 95% purity. The second key step is the resolution of the racemic ester by a highly enantioselective lipase from Pseudomonas sp. The immobilized enzyme carried out the transesterification reaction to nearly full conversion (46% out of 50%) with an enantiomeric excess of >96%. The enzymatic reaction was accomplished in a batch system as well as in a fluidized bed column. The reaction was found to be inhibited by accumulation of the product and to a lesser extent, by the aldehyde. The separation of the enantiomerically pure alcohol from the undesired ester was performed by chromatographic techniques, as well as by extraction with hexane. The final racemization step of the (R)-ester was easily attained with the use of triethylamine in diisopropyl ether or toluene. The process was shown to be feasible on a gram scale and shows potential for scale up.
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