Enantiodivergent Synthesis of Halofuginone by Candida antarctica Lipase B (CAL-B)-Catalyzed Kinetic Resolution in Cyclopentyl Methyl Ether (CPME)

Abstract

The synthesis of both enantiomers of a key intermediate in the synthesis of halofuginone was accomplished by a Candida antarctica lipase B (CAL-B)-catalyzed kinetic resolution of the corresponding racemate. When the resolution was carried out in the versatile solvent cyclopentyl methyl ether (CPME) using p-chlorophenylbutyrate (PCPB) as the acylating reagent, the highest enantiomeric ratio (E) values were measured, and highly enantioenriched (95% ee) compounds could be obtained in a single iteration. As an example, one of the two enantiomers was used as a starting material to prepare (+)-halofuginone in a three-step procedure.

Key words

biocatalysis - lipase - kinetic resolution - halofuginone

Publication History

Received: 04 May 2021

Accepted after revision: 14 May 2021

Accepted Manuscript online:
07 June 2021

Article published online:
17 June 2021

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