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Chemoenzymatic Synthesis in Flow Reactors: A Rapid and Convenient Preparation of Captopril

By De Vitis, Valerio; Dall'Oglio, Federica; Pinto, Andrea; De Micheli, Carlo; Molinari, Francesco; Conti, Paola; Romano, Diego; Tamborini, Lucia

Published on CMKC

Abstract

The chemoenzymatic flow synthesis of enantiomerically pure captopril, a widely used antihypertensive drug, is accomplished starting from simple, inexpensive, and readily available reagents. The first step is a heterogeneous biocatalyzed regio- and stereoselective oxidation of cheap prochiral 2-methyl-1,3-propandiol, performed in flow using immobilized whole cells of Acetobacter aceti MIM 2000/28, thus avoiding the use of aggressive and environmentally harmful chemical oxidants. The isolation of the highly hydrophilic intermediate (R)-3-hydroxy-2-methylpropanoic acid is achieved in-line by using a catch-and-release strategy. Then, three sequential high-throughput chemical steps lead to the isolation of captopril in only 75 min. In-line quenching and liquid–liquid separation enable breaks in the workflow and other manipulations to be avoided.

Journal

ChemistryOpen. Volume 6, 2017, 668-673

DOI

10.1002/open.201700082

Type of publication

Peer-reviewed journal

Affiliations

  • University of Milan

Article Classification

Research Article

Classification Areas

  • API

Tags