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

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.

Automated summary

The synthesis of both enantiomers of a key intermediate in the synthesis of halofuginone was achieved through a Candida antarctica lipase B (CAL-B)-catalyzed kinetic resolution, using p-chlorophenylbutyrate (PCPB) as the acylating reagent in the versatile solvent cyclopentyl methyl ether (CPME). High enantiomeric ratio (E) values were obtained, with a single iteration yielding highly enantioenriched (95% ee) compounds, facilitating the preparation of (+)-halofuginone in a three-step procedure.