Cardenolide analogues. 2. 22-Methylenecard-14-enolides

22-Methylene-3beta-hydroxy-5beta,20(S)-card-14-enolide (11) and 22-methylene-3beta-hydroxy-5beta,20(R)-card-14-enolide (12) were synthesized from digitoxin (1). Attempts to prepare the 14beta-hydroxy-22-methylene analogues were unsuccessful. The 20(R) isomer (12) was found in Na+, K+-ATPase inhibition studies to be twice as active as 14-dehydrogitoxigenin (17). The 20(S) isomer (11) was significantly less active than 17. The hydrolysis of steroid 3beta-tert-butyldimethysilyl ethers was also found to be much more difficult than with nonsteroids.