Efficient Chemo-Enzymatic Flow Synthesis of High Value Amides and Esters

被引：25

作者：

Annunziata, Francesca ^{[1
]}

Letizia Contente, Martina ^{[2
]}

Betti, Daniele ^{[1
]}

Pinna, Cecilia ^{[1
]}

Molinari, Francesco ^{[3
]}

Tamborini, Lucia ^{[1
]}

Pinto, Andrea ^{[3
]}

机构：

[1] Univ Milan, Dept Pharmaceut Sci DISFARM, Via Mangiagalli 25, I-20133 Milan, Italy

[2] Univ Nottingham, Sch Chem, Univ Pk, Nottingham NG7 2RD, England

[3] Univ Milan, Dept Food Environm & Nutr Sci DeFENS, Via Celoria 2, I-20133 Milan, Italy

来源：

CATALYSTS | 2020年 / 10卷 / 08期

关键词：

flow chemistry; biocatalysis; immobilisation; active pharmaceutical ingredients; flow hydrogenation; BIOCATALYSIS; CATALYST; ENZYME; TOOLS; WATER;

D O I：

10.3390/catal10080939

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

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 fromMycobacterium 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.

引用

页数：8

共 31 条

[1]

Abdullaev M.G., 2001, PHARM CHEM J, V35, P556, DOI [10.1023/A:1014762419378, DOI 10.1023/A:1014762419378]

[2]

ALFONSI K, 2008, GREEN CHEM, V0010, P00031, DOI DOI 10.1039/B711717E

[3]

[Anonymous], 2015, ANGEW CHEM INT EDIT, DOI DOI 10.1002/ANIE.201409318

[4]

BAUMANN M, 2015, BEILSTEIN J ORG CHEM, V0011, P01194, DOI DOI 10.3762/bjoc.11.134

[5]

Baumann M., 2020, ORG PROCESS RES DEV, DOI [10.1021/acs.oprd.9b00524, DOI 10.1021/ACS.OPRD.9B00524]

[6]

BRITTON J, 2018, CHEM SOC REV, V0047, P05891

[7]

CONTENTE ML, 2019, GREEN CHEM, V0021, P03263, DOI DOI 10.1039/C9GC01374A

[8]

CONTENTE ML, 2018, ADV SYNTH CATAL, V0360, P04814, DOI DOI 10.1002/adsc.201801061

[9]

CONTENTE ML, 2020, J FLOW CHEM, V0010, P00235, DOI DOI 10.1007/s41981-019-00063-8

[10]

DALLOGLIO F, 2017, CATAL COMMUN, V0093, P00029, DOI DOI 10.1016/j.catcom.2017.01.025

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