强心苷。6. 羟基洋地黄毒苷元C16乙酸酯、甲酸酯、甲氧基碳酸酯及洋地黄毒糖苷。合成及钠钾ATP酶抑制活性。

Cardiac glycosides. 6. Gitoxigenin C16 acetates, formates, methoxycarbonates, and digitoxosides. Synthesis and Na+,K+-ATPase inhibitory activities.

作者信息

Hashimoto T, Rathore H, Satoh D, Hong G, Griffin J F, From A H, Ahmed K, Fullerton D S

出版信息

J Med Chem. 1986 Jun;29(6):997-1003. doi: 10.1021/jm00156a017.

PMID:3012087

Abstract

A series of 17 gitoxigenin 16 beta-formates, acetates, and methoxycarbonates was synthesized, including their 3 beta-acetates, formates, and digitoxosides. A 16 beta-formate group was generally found to increase activity 30 times, a 16 beta-acetate group 9-12 times, while a 16 beta-methoxycarbonate decreased activity by two-thirds. 3 beta-Formates and acetates had little effect on activity by themselves, but sometimes reduced the activity-increasing properties of 16 beta-formates and acetates. A 3 beta-digitoxoside increases the activity of gitoxigenin by 15 times, but the effect is less if the 16 beta-group is esterified. And finally, a 16-one decreases activity dramatically. These data suggest an important role for C16 esters and possibly the presence of a separate binding site on Na+,K+-ATPase corresponding to the cardenolide C16 position.

摘要

合成了一系列17种洋地黄毒苷元16β-甲酸酯、乙酸酯和甲氧基碳酸酯，包括它们的3β-乙酸酯、甲酸酯和洋地黄毒糖苷。一般发现16β-甲酸酯基团可使活性增加30倍，16β-乙酸酯基团可使活性增加9至12倍，而16β-甲氧基碳酸酯则使活性降低三分之二。3β-甲酸酯和乙酸酯本身对活性影响不大，但有时会降低16β-甲酸酯和乙酸酯的活性增强特性。3β-洋地黄毒糖苷可使洋地黄毒苷元的活性增加15倍，但如果16β-基团被酯化，效果会减弱。最后，16-酮会显著降低活性。这些数据表明C16酯具有重要作用，并且可能在Na⁺,K⁺-ATP酶上存在一个与强心苷C16位置相对应的独立结合位点。