强心甾内酯类似物。2. 22-亚甲基强心-14-烯内酯。

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

作者信息

Fullerton D S, Gilman T M, Pankaskie M C, Ahmed K, From A H, Duax W L, Rohrer D C

出版信息

J Med Chem. 1977 Jun;20(6):841-4. doi: 10.1021/jm00216a022.

Abstract

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.

摘要

以洋地黄毒苷（1）合成了22-亚甲基-3β-羟基-5β,20(S)-强心甾-14-烯内酯（11）和22-亚甲基-3β-羟基-5β,20(R)-强心甾-14-烯内酯（12）。制备14β-羟基-22-亚甲基类似物的尝试未成功。在Na⁺,K⁺-ATP酶抑制研究中发现，20(R)异构体（12）的活性是14-脱氢洋地黄毒苷元（17）的两倍。20(S)异构体（11）的活性明显低于17。还发现甾体3β-叔丁基二甲基甲硅烷基醚的水解比非甾体的水解困难得多。