Herstellung von ungesättigten Lactonen der Steroid‐Reihe, IV¹⁾ Synthese von Uzarigenin

Abstract

The 10-formyl group in k-strophanthidine (1) reacts with (diethoxyphosphoryl)acetonitrile/ sodium hydride or ethyl (diethoxyphosphoryl)acetate/sodium hydride under non-prototropic reaction conditions via PO-activated o l e h t i o n to form the corresponding cardenolides 4 and 6, respectively, bearing two additional C-atoms in position 19, without impairing the 14@-hydroxy-17(3-butenolide system essential for cardiac activity. Under prototropic conditions, however, the butenolide ring is transformed chemically. The glycosides 12,14, and 16 are obtained by glycosidation of the 3-hydroxy group of 6 and 4 according to the KoenigsKnorr or "glycal'' process, and subsequent saponification of the sugar acetate groups. -Reaction of ethoxyethynyllithium and of methyllithium with the 10-fonnyl group of 3-0-(tetrahydro-2-pyranyl)-k-strophanthidine (17) and subsequent reactions leads to 6, and to the cardenolides 20 and 22, respectively, bearing an additional methyl group at C-19. -The glycosides 12 and 14 show the highest cardiac activity i n isolated guinea pig hearts.

Synthese von 4‐[3β, 14‐Dihydroxy‐5β, 14β‐androstan‐17β‐yl]‐3‐pyrrolin‐2‐on (Hothesimogenin). Partialsynthetische Versuche in der Reihe der Herzgifte, 11. Mitteilung

“…Als Ausgangsmaterialien werden dabei leicht isolierbare oder leicht erhaltliche Genine [2], Glykoside oder Pregnen-Derivate [3] [4] verwendet.…”

Stereoselective semisynthesis of uzarigenin and allo-uzarigenin

“…However, the stereochemistry at C-14 was not further discussed. 7 The same applies to Khristulas' uzarigenin (2) semisynthesis, which started from 3-acetoxy-5-pregn-16-en-20-one and did not provide any direct proof of the configuration of the synthesized compounds. 8 Emil Angliker managed to introduce the 14-hydroxy group but struggled with the configuration at C-17 and therefore could only report the synthesis of allo-uzarigenin.…”

Control of the stereochemistry of C14 hydroxyl during the total synthesis of withanolide E and physachenolide C

“…A number of strategies for the stereoselective introduction of a hydroxyl group at the C14 position of steroids have been described; however they mainly lead to the b-OH conguration. These include hydrobromination of D 14-15 steroid followed by removal of bromine from C-15; [12][13][14][15] Norish type II reaction of C-12 ketosteroids, 16 metal catalysed hydration of D 14-15 steroid, 17 metal 18,19 or enzyme catalysed direct conversion of C14-H to C14-OH, [20][21][22] and through tandem construction of steroid's ring D. 23 In our synthetic path, we opted for selective introduction of C-14a hydroxylation via epoxidation of D 14-15 , followed by regioselective reduction at C15 to generate the corresponding alcohol ( Fig. 1).…”