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 Candida antarctica lipase B-catalyzed kinetic resolution of the corresponding racemate. When the resolution was carried out in the versatile and eco-friendly solvent cyclopentyl methyl ether (CPME) using PCPB (p-chlorophenylbutyrate) 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.

Asymmetric Reduction of Cyclic Imines by Imine Reductase Enzymes in Non‐Conventional Solvents

“…However, to the best of our knowledge, the use of DESs in bioreduction processes with isolated enzymes has been limited to ketoreductases (KREDs) [8f] and alcohol dehydrogenases (ADHs) [8j] . Drawing on our interest in both biocatalysis [16] and the use of non‐conventional solvents, [5a,7a,9a,16a,h,17] we decided to investigate the efficiency of an emergent class of NADPH‐dependent enzymes, namely imine reductases (IREDs), in the reduction of cyclic imines using non‐conventional solvents [18] . This family of oxidoreductases was discovered in 2010 by Mitsukura and co‐workers [19] and has since gained increasing attention because it offers a promising biocatalytic approach to obtaining primary, secondary and tertiary chiral amines, which are key intermediates in the synthesis of several biological active compounds (Figure 1).…”