Investigations on steroids. XL. 14,19-Dihydroxy-14β,17α-cortexone and other compounds derived from 17α-strophanthidol

Abstract

As continuation of our early research on the synthesis of steroid hormone analogues of the 14β,17α-pregnane series (1–5,7), the conversion of 17α-strophanthidol (5) into 14,19-dihydroxy-14β,17α-cortexone (19) has been achieved.—In basic investigations the 3,19-diacetate (6), the 3-monoacetate (7), and the 19-monoacetate (8) of 5 were studied. Using independent routes 5 and 8 were converted into 3-oxo-14,19-dihydroxy-Δ4,2O(22)-14β,17α-cardadienolide(11).—In preparing 19,5 was first subjected to ozono-lysis yielding 3β,5,14,19,21-pentahydroxy-5β,14β,17α-pregnan-20-one (13) which was characterized as the 3,19,21-triacetate (14). Selective oxidation of 13 with N-bromoacetamide gave 5,14,19,21-tetrahydroxy-5β,14β,17α-pregnane-3,20-dione (18) which by treatment with Girard′s reagent T underwent dehydration yielding 19.—In degradation studies, oxidation of 13 with sodium periodate gave 3β,5,14,19-tetrahydroxy-5β,14β,17α-etianic acid (15) which was characterized as the methyl ester (16) and the corresponding 3,19-diacetate (17). In a similar fashion, oxidation of 19 with sodium periodate gave 3-oxo-14,19-dihydroxy-Δ 4-14β,17α-etienic acid (21) which was characterized as the methyl ester (22).—Regarding compounds 13 and 14 there are discrepancies with findings reported in the literature earlier. A discussion of this matter is included in this paper.14,19-Dihydroxy-14β,17α-cortexone (19) appears to exhibit sodium excreting activity in the adrenal-ectomized rat.