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Short and Efficient Chemoenzymatic Syntheses of non‐Natural (−)‐Muscarine and (+)‐ allo ‐Muscarine from Cyano‐Sugar Precursors Catalyzed by Immobilized Burkholderia cepacia Lipase
Author(s) -
Carnero Alejandro,
Sanghvi Yogesh S.,
Gotor Vicente,
Fernández Susana,
Ferrero Miguel
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201600749
Subject(s) - chemistry , lipase , burkholderia , hydrolysis , organic chemistry , sugar , hydrogenolysis , catalysis , enzyme , bacteria , biology , genetics
Enantiopure (2 R )‐configured non‐natural (−)‐muscarine and (+)‐ allo ‐muscarine were efficiently synthesized by a chemoenzymatic approach from an easily accessible cyano‐sugar available on a large‐scale. The key enzymatic hydrolysis step was accomplished by immobilized Burkholderia cepacia lipase (also known as Pseudomonas cepacia lipase, PSL‐IM). The PSL‐IM‐mediated regioselective hydrolysis of the 5‐ O ‐toluoyl ester group in α‐ and β‐cyano‐sugars, furnished 3‐ O ‐toluoyl‐α‐cyano‐sugar and 3‐ O ‐toluoyl‐β‐cyano‐sugar, respectively, with total selectivity and in excellent yields. To demonstrate the industrial utility of this method, 3‐ O ‐toluoyl‐β‐cyano‐sugar was synthesized on a 10 g scale using PSL‐IM and the catalyst was reused. A key feature of the synthesis route described herein is the simultaneous hydrogenolysis of a tosyl group, reduction of a nitrile and deprotection of a toluoyl group using LiAlH 4 in a one‐pot procedure. This study offers a green protocol for synthesis of two muscarine derivatives in high yields employing a concise four‐step strategy.