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Chemoenzymatic Synthesis of Luliconazole Mediated by Lipases
Author(s) -
Fonseca Thiago de S.,
Lima Lara D.,
de Oliveira Maria da C. F.,
de Lemos Telma L. G.,
Zampieri Davila,
Molinari Francesco,
de Mattos Marcos C.
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800250
Subject(s) - chemistry , kinetic resolution , lipase , yield (engineering) , hydrolysis , biocatalysis , selectivity , stereochemistry , organic chemistry , enzyme , enantioselective synthesis , catalysis , reaction mechanism , materials science , metallurgy
A straightforward chemoenzymatic synthesis of luliconazole has been developed. The key step involved the preparation of the enantiomerically pure β‐halohydrin (1 S )‐2‐chloro‐1‐(2,4‐dichlorophenyl)‐1‐ethanol through kinetic resolution of the corresponding racemic acetate. This was achieved by a hydrolytic approach, mediated by the lipase from Thermomyces lanuginosus or Novozym 435®. The latter enzyme proved to be a robust biocatalyst for the kinetic resolution, and the ( S )‐β‐halohydrin was obtained with high selectivity ( ee > 99 %, E > 200) after just 15 min, at 45 °C. It could be reused five times with maintenance of high values of both conversion and enantioselectivity. Subsequently, the ( S )‐β‐halohydrin was subjected to a mesylation reaction; the mesylated derivative reacted with 1‐cyanomethylimidazole in the presence of CS 2 to give luliconazole in 43 % yield with >99 % ee .