Gobbini M, Benicchio A, Marazzi G, Padoani G, Torri M, Melloni P
Prassis Istituto di Ricerche Sigma-Tau, Settimo Milanese, Italy.
Steroids. 1996 Oct;61(10):572-82. doi: 10.1016/s0039-128x(96)00117-1.
The synthesis of seco-D and D-homo digitalis derivatives, from the carda-14,20(22)-dienolide 1, is described. Selective ozonolysis gave the seco-D 14-ketoaldehyde 2a. Modification of the two carbonyl groups and of the alpha, beta-unsaturated lactone ring of the seco-D 14-ketoaldehyde 2a allowed preparation of derivatives with a broad range of binding affinity to the Na+, K(+)-ATPase receptor. Some of the seco-D derivatives (10, 11b, and 13b) showed a binding affinity similar to that of digitoxigenin, demonstrating that the D-ring is not essential for recognition by the digitalis receptor. In the class of D-homo derivatives the highest binding value, about 15 times lower than that of digitoxigenin, was that of the C/D cis compound 29b; the C/D trans analog 28b showed a 7-fold decrease in binding affinity, indicating that the C/D configuration plays an important role in D-homo derivatives as in the classical digitalis compounds.
本文描述了从强心甾-14,20(22)-二烯内酯1合成开环-D和D-高洋地黄毒苷衍生物的过程。选择性臭氧分解得到开环-D 14-酮醛2a。对开环-D 14-酮醛2a的两个羰基和α,β-不饱和内酯环进行修饰，能够制备出对Na +, K(+)-ATP酶受体具有广泛结合亲和力的衍生物。一些开环-D衍生物（10、11b和13b）显示出与洋地黄毒苷元相似的结合亲和力，这表明D环对于洋地黄受体的识别并非必不可少。在D-高衍生物类别中，结合值最高的是C/D顺式化合物29b，约比洋地黄毒苷元低15倍；C/D反式类似物28b的结合亲和力降低了7倍，表明C/D构型在D-高衍生物中与在经典洋地黄化合物中一样起着重要作用。
