Short and Efficient Chemoenzymatic Syntheses of non‐Natural (−)‐Muscarine and (+)‐allo‐Muscarine from Cyano‐Sugar Precursors Catalyzed by Immobilized Burkholderia cepacia Lipase

Abstract

AbstractEnantiopure (2R)‐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 LiAlH4 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.magnified image