BioChem - DOS

Studies on the dynamic resolution of Crizotinib intermediate

Bioorganic & medicinal chemistry

de Franç a, Alexandre da S.; Silva, Marcus V.M.; Neves, Rebeca V.; de Souza, Stefania P.; Leã o, Raquel A.C.; Monteiro, Carlos M.; Rocha, Â ngelo; Afonso, Carlos A.M.; de Souza, Rodrigo O.M.A.

<P><B>Abstract</B></P> <P>Crizotinib is an anti-cancer agent approved for treatment of non-small cell lung carcinoma. Retrosynthetic analysis revels 1-(2,6-dichloro-3-fluorophenyl)ethanol as an important intermediate, which can be made available by different biocatalytic approaches. Herein we report our results on the kinetic and dynamic resolution towards the desired chiral intermediate for Crizotinib synthesis. The results obtained show that very good conversions and high selectivity could be obtained for the kinetic resolution (45% conv. and <I>E</I> >200) while dynamic kinetic resolution under continuous-flow conditions afforded the desired product in 57% conversion and 98% e.e.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

2018

Elsevier

0968-0896

1464-3391

26

7

pp.1333-1337

10.1016/j.bmc.2017.07.024

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART84866432

Kinetic resolution; Lipases; Dynamic resolution; Crizotinib; Continuous-flow