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.
Chemoenzymatic Synthesis of Luliconazole Mediated by Lipases / T.D.S. Fonseca, L.D. Lima, M.D.C.F. de Oliveira, T.L.G. de Lemos, D. Zampieri, F.E. Molinari, M.C. de Mattos. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 18(2018 May 15), pp. 2110-2116. [10.1002/ejoc.201800250]
Chemoenzymatic Synthesis of Luliconazole Mediated by Lipases
F.E. MolinariPenultimo
Supervision
;
2018
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
Artigo luliconazole 16.11.2017_fm.pdf
accesso aperto
Tipologia:
Pre-print (manoscritto inviato all'editore)
Dimensione
596.11 kB
Formato
Adobe PDF
|
596.11 kB | Adobe PDF | Visualizza/Apri |
Fonseca_et_al-2018-European_Journal_of_Organic_Chemistry (1).pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
905.52 kB
Formato
Adobe PDF
|
905.52 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.