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14) and requires fewer critical conserved nodes in the top half of the TM bundle (Supplementary Fig

For this purpose, 4-chloro-3-hydroxybutyronitrile is synthesized from epichlorohydrin in an aqueous hydrogen cyanide solution, 4-chloro-3-hydroxy butyric acid alkyl ester is then synthesized from the 4-chloro-3-hydroxybutyronitrile in the presence of an alcohol and a sulfuric acid catalyst, and the racemic 4-chloro-3 -hydroxy butyric acid alkyl ester is hydrolyzed in an aqueous solution using an enzyme, thereby preparing (R)-4-chloro-3-hydroxy butyric acid alkyl ester

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