Preparation method for resolving optical active cyan alcohol by enzyme process

Abstract

The invention publishes a kind preparation methods to aplit optical activity cyan alcohol by enzyme method. The approach follows this. 1, dissolve recemism cyan alcohol in organic solvent and then add aliphatic alcohol. The mol ratio of cyan alcohol ester and aliphatic alcohol is 0.1-1:20 and mix them fully. 2, book the alcoholysis reaction of cyan alcohol ester under the condition of enzyme catalysis in reaction system and then keep the reaction as well as agitating in temperature of 0-70 degree. The ratio of cyan alcohol ester and enzymatic is 0.001-100mol every cyan ester to 1 kilogram enzymatic. 3, filter the reaction fluid and recycle enzymatic to get S-cyan alcohol with capability of high optically active. The invention has many advantages, such as, reactive selection is good, conversion is high and the S-cyan alcohol optical purity is high and its application temperature is wide.

Description

technical field [0001] The invention relates to a preparation method for enzymatically splitting optically active cyanohydrins. Background technique [0002] Optically active cyanohydrins are an important class of chiral intermediates, which are easily converted into chiral substances such as β-amino alcohols, α-hydroxy acids, α-hydroxy ketones, and α-amino acids. and other fields have broad application prospects (Effenberger, F. Angew. Chem. Int. Ed. Engl., 1994, 33, 1555-1564). S-α-cyano-3-phenoxybenzyl alcohol and S-α-cyano-4-fluoro-3-phenoxybenzyl alcohol (S-cyanohydrin, formula 1) are mainly used in the synthesis of pyrethroid insecticides. Pyrethroid insecticides with cyanohydrin as the alcohol composition structure greatly improve the insecticidal activity and photostability of pyrethroids due to the introduction of phenylene ether groups and cyano groups. It has been proved that if the acid or alcohol part of a pyrethroid contains a chiral center, its stereo confi...

AI Technical Summary

Problems solved by technology

The enzymatic resolution method of cyanohydrin has multiple, can utilize easily obtained R-alcohol nitrilase to directly decompose R-cyanohydrin and realize resolution, but 50% cyanohydrin is decomposed and wasted (as patent No. DE4139987 and US5241087 method described in); can also be resolved using lipase-catalyzed selective esterification (Hsu, S.H. et al., Tetrahedron Letter, 1990, 31, 6403-6406; Inagaki, M. et al., J.Am.Chem.Soc ., 1991,113,9360-9361), shortcoming is that the product S-cyanohydrin ester obtained needs to be converted into corresponding S-cyanohydrin by reaction again, and the enantiomeric purity of product is generally not very high; Be converted into ester and utilize lipase or esterase selective hydrolysis to carry out resolution (as the method described in JP59130188 and US4985365 as the patent No.), but because the solubility of cyanohydrin ester in aqueous solution is not high, and product cyanohydrin is in aqueous solution easy to decompose in medium, so it is not conducive to large-scale production

In addition, there is a common method of diastereomer resolution, that is, enantiomers react with a chiral resolution reagent to generate a pair of diastereomers, and then separate according to the difference in the physicochemical properties of the diastereomers (as disclosed in the patent No. is the method described in CN1205003), and the main disadvantage is that the steps are complicated, the resolution process is tedious, the required reagents are expensive, and the product purity is lower

Images