CC BY-NC-ND 4.0 · SynOpen 2021; 05(02): 145-151
DOI: 10.1055/a-1523-6428
paper

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

a  Dipartimento di Chimica ‘Ugo Schiff’, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy
,
b  Dipartimento di Chimica, Università degli Studi di Torino, Via Pietro Giuria 7, 10125 Torino, Italy
,
c  Huvepharma Italia, Via Lepetit 142, 12075 Garessio (CN), Italy
,
Dina Scarpi
a  Dipartimento di Chimica ‘Ugo Schiff’, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy
,
Cristina Prandi
b  Dipartimento di Chimica, Università degli Studi di Torino, Via Pietro Giuria 7, 10125 Torino, Italy
,
a  Dipartimento di Chimica ‘Ugo Schiff’, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy
› Author Affiliations
This research was supported by Huvepharma® Italia and by the University of Florence.


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.

Supporting Information



Publication History

Received: 04 May 2021

Accepted after revision: 14 May 2021

Publication Date:
07 June 2021 (online)

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