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.
Chemoenzymatic synthesis in flow reactors: a rapid and convenient preparation of Captopril / V. De Vitis, F. Dall’oglio, A. Pinto, C. De Micheli, F.E. Molinari, P. Conti, D. Romano, L. Tamborini. - In: CHEMISTRYOPEN. - ISSN 2191-1363. - 6:5(2017 Oct), pp. 668-673. [10.1002/open.201700082]
Chemoenzymatic synthesis in flow reactors: a rapid and convenient preparation of Captopril
V. De VitisPrimo
;F. Dall’OglioSecondo
;A. Pinto;C. De Micheli;F.E. Molinari;P. Conti;D. Romano
Penultimo
;L. Tamborini
Ultimo
2017
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.File | Dimensione | Formato | |
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