A flow-based chemo-enzymatic synthesis of selected APIs (i.e., butacaine, procaine and procainamide) has been developed. A bioreactor made of MsAcT, a versatile acyltransferase from Mycobacterium smegmatis, immobilised on glyoxyl–garose, was exploited to efficiently prepare amide and ester intermediates in gram scale. Immobilised MsAcT was employed in pure organic solvent, demonstrating high stability and reusability. In-line purification of the key intermediates using polymer-bound sulphonyl chloride was added after the bioreactor, enhancing the automation of the process. A final hydrogenation step using the H-Cube reactor was further carried out to obtain the selected APIs in excellent yields (>99%), making the process fast, safe and easily handled.

Efficient chemo-enzymatic flow synthesis of high value amides and esters / F. Annunziata, M.L. Contente, D. Betti, C. Pinna, F. Molinari, L. Tamborini, A. Pinto. - In: CATALYSTS. - ISSN 2073-4344. - 10:8(2020 Aug), pp. 939.1-939.8. [10.3390/catal10080939]

Efficient chemo-enzymatic flow synthesis of high value amides and esters

Annunziata F.;Contente M. L.;Pinna C.;Molinari F.;Tamborini L.;Pinto A.
2020-08

Abstract

A flow-based chemo-enzymatic synthesis of selected APIs (i.e., butacaine, procaine and procainamide) has been developed. A bioreactor made of MsAcT, a versatile acyltransferase from Mycobacterium smegmatis, immobilised on glyoxyl–garose, was exploited to efficiently prepare amide and ester intermediates in gram scale. Immobilised MsAcT was employed in pure organic solvent, demonstrating high stability and reusability. In-line purification of the key intermediates using polymer-bound sulphonyl chloride was added after the bioreactor, enhancing the automation of the process. A final hydrogenation step using the H-Cube reactor was further carried out to obtain the selected APIs in excellent yields (>99%), making the process fast, safe and easily handled.
Active pharmaceutical ingredients; Biocatalysis; Flow chemistry; Flow hydrogenation; Immobilisation
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/10 - Chimica degli Alimenti
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/768444
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