On Cardioactive Steroids. XVI. Stereoselective β-Glycosylation of Digitoxose: The Synthesis of Digitoxin†

Two methods for stereoselective β-glycosylation of digitoxose were developed. The first achieved stereocontrol by a 1,3-participation of a N-methylurethane group under acid catalysis. The second utilized mercuric-ion catalyzed cleavage of thioglycosides and a 1,3-participation of a p-methoxybenzoyl group in a neutral medium. The first highly stereoselective and quite efficient synthesis of digitoxin (C7) was achieved by a combination of these methods. The furyl-substituted precursor IV of digitoxigenin (Scheme 1) was used as aglycone, and the furan group was converted to the unsaturated lactone of digitoxin by our known oxidation procedure (m-chloroperbenzoic acid/NaBH4) after the assembly of the carbohydrate portion of the molecule and its deblocking was completed.

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