A straightforward chemoenzymatic synthesis of luli- conazole has been developed. The key step involved the preparation of the enantiomerically pure beta-halohydrin (1S)-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 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)-beta-halohydrin was sub- jected to a mesylation reaction; the mesylated derivative re- acted with 1-cyanomethylimidazole in the presence of CS2 to give luliconazole in 43 % yield with >99 % ee.
|Titolo:||Chemoenzymatic Synthesis of Luliconazole Mediated by Lipases|
MOLINARI, FRANCESCO ENZO (Penultimo)
|Parole Chiave:||biocatalysis; chemoenzymatic synthesis; stereoselectivity; enzymatic reaction|
|Settore Scientifico Disciplinare:||Settore CHIM/11 - Chimica e Biotecnologia delle Fermentazioni|
|Data di pubblicazione:||15-mag-2018|
|Digital Object Identifier (DOI):||10.1002/ejoc.201800250|
|Appare nelle tipologie:||01 - Articolo su periodico|