One‐Pot Oxidation–Hydrocyanation Sequence Coupled to Lipase‐Catalyzed Diastereoresolution in the Chemoenzymatic Synthesis of Sugar Cyanohydrin Esters

Abstract

Abstract A three‐step, one‐pot synthesis and diastereoresolution sequence is described in anhydrous toluene starting from methyl α‐ D ‐2,3,4‐tri‐ O ‐acetylgalacto‐ ( 1a ), ‐manno‐ ( 1b ) and ‐glucopyranosides ( 1c ). The reaction sequence, including consecutive transformations through the aldehyde [PhI(OAc) 2 , 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO)] and cyanohydrin [basic resin or ( R )‐oxynitrilase] into the (6 R )‐cyanohydrin ester (lipase) is shown to proceed in a one‐pot cascade, except that the basic resin (when used) should be removed before the addition of the enzymatic acylation reagents. We have shown that the effective transformation of 1a (75 % reaction yield) through labile intermediates gives the stable (6 R )‐cyanohydrin butanoate (85 % de ). Further diastereomeric purification by chromatography is possible, although the product is already of high diastereopurity. (6 R )‐Cyanohydrin esters are obtained through acylation with Burkholderia cepacia lipase. The (6 S )‐ester ( de 99 %) is produced by Candida rugosa lipase when the sequence is started from 1c whereas the other sugar derivatives are less suited to the reaction with lipase.