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

• Published in: SynOpen
• Main Authors: Elisa De Marchi, Davide Arnodo, Elia Maffeis, Dina Scarpi, Cristina Prandi, Ernesto G. Occhiato
• Format: Article in Journal/Newspaper
• Language: English
• Published: Georg Thieme Verlag KG 2021
• Subjects: biocatalysis; lipase; kinetic resolution; halofuginone; Chemistry; QD1-999; Antarc*; Antarctica
• Online Access: https://doi.org/10.1055/a-1523-6428; https://doaj.org/article/29ab8c99137548199062a896a8204827

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.