Stereoselective Synthesis of New Simplified Digitalis-Like Compounds from (+)-(3aS,7aS)-3a-Hydroxy-7a-Methylperhydroinden-1,5-Dione

Cardiac glycosides of Digitalis species are well known heart-stimulating drugs, clinically used for treatment of congestive heart failure.2 In the steroidal moiety of the aglycons (cardenolides) the C/D cis ring junction, the 14b-OH and the 17b-butenolide could be recognized as three peculiar features for a potent pharmacological action, while the A/B ring junction can vary from cis (e.g. digitoxigenin) to trans (e.g. uzarigenin) (Fig. 1) without a dramatic loss of activity. As a part of our work aimed at searching new digitalis-like compounds with an improved pharmacological profile, we synthesized compound 9 (Fig. 1) in which the C/D part of the molecule was maintained while the A/B part was simplified in a 5b-cyclohexyl substituent.