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

Elisa De Marchi; Davide Arnodo; Elia Maffeis; Dina Scarpi; Cristina Prandi; Ernesto G. Occhiato

doi:10.1055/a-1523-6428

SynOpen, Table of Contents

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)

Elisa De Marchi

^aDipartimento di Chimica ‘Ugo Schiff’, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy

,

Davide Arnodo

^bDipartimento di Chimica, Università degli Studi di Torino, Via Pietro Giuria 7, 10125 Torino, Italy

,

Elia Maffeis

^cHuvepharma Italia, Via Lepetit 142, 12075 Garessio (CN), Italy

,

Dina Scarpi

^aDipartimento di Chimica ‘Ugo Schiff’, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy

,

Cristina Prandi

^bDipartimento di Chimica, Università degli Studi di Torino, Via Pietro Giuria 7, 10125 Torino, Italy

,

Ernesto G. Occhiato ∗

^aDipartimento di Chimica ‘Ugo Schiff’, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy

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Abstract

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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

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References

References and Notes

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