Regioselective Esterification of Cardiac Glycosides Catalyzed by Novozym 435 and Lipase PS in Organic Solvents

Abstract

The enzymatic acetylation in the organic solvents of a number of the important bioactive cardiac glycosides was investigated. With the bufanolide proscillaridin A and the cardenolide lanatoside C, acylation, as expected, occurred at the secondary 4′-OH of the rhamnopyranosyl unit of the former (by the action of Novozym 435 lipase) and the primary 6′′′′-OH of the terminal glucopyranosyl unit of the latter (best results obtained by the action of the lipase PS). Only lipase PS was found to be able to acylate the cardenolides digitoxin and digoxin at the 4‴-OH of their terminal digitoxose unit. The corresponding monoacetyl derivatives, both of which are commercialized drugs, could be isolated with good yields. The investigation of the Novozym 435-catalyzed acetylation of free D-digitoxose provided a possible explanation for the inability of this lipase to acylate digitoxin and digoxin.

Keywords

• cardiac glycosides
• Novozym 435
• Lipase ps
• biocatalysis
• regioselective esterification
• organic solvents