Open AccessChemoenzymatic Synthesis in Flow Reactors: A Rapid and Convenient Preparation of Captopril
Author(s) -
De Vitis Valerio,
Dall'Oglio Federica,
Pinto Andrea,
De Micheli Carlo,
Molinari Francesco,
Conti Paola,
Romano Diego,
Tamborini Lucia
Publication year - 2017
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201700082
Subject(s) - chemistry , captopril , flow chemistry , combinatorial chemistry , reagent , chemical synthesis , stereoselectivity , organic chemistry , chromatography , biochemistry , catalysis , medicine , blood pressure , in vitro , radiology
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.