Synthesis of 19-noraldosterone, a potent mineralocorticoid.
19-Noraldosterone has been prepared for biological re-evaluation through an extension of a recent synthesis of 19-hydroxyaldosterone: 21-hydroxy-6 beta,19-epoxy-4-pregnene-3,20-dion-20-ethylene ketal-18,11 beta-lactone (1a) was acetylated and then reduced with zinc-acetic acid-isopropanol to the 19-ol 2b. Treatment with sodium acetate transposed the double bond into conjugation, and 2a thus obtained was oxidized with pyridinium chlorochromate to the 19-oxo compound 3. Decarbonylation to the 19-nor lactone 4 was effected by heating with alkali. Protection of the C-3 carbonyl was achieved by ketalization and the resulting mixture of the 5-ene and 5(10)-ene ketals 5 was reduced with DIBAH to the corresponding mixture of the hemiacetals 6. Acid hydrolysis of the latter afforded 19-noraldosterone (7), accompanied by the 18,21-anhydro ketal 8. 19-Noraldosterone in the solid state exists in the cyclic form 7b, which appears to be also the predominant isomer present under conditions of mass spectrometry. [1H]NMR indicates that in chloroform 19-noraldosterone exists mostly as an equilibrium mixture of structures 7a and 7b. Sodium periodate oxidation furnished the gamma-etiolactone 9, confirming the 17 beta configuration in 7.
D000450:Aldosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001001:Anura; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D008722:Methods; D008901:Mineralocorticoids / Q000138:chemical synthesis*; D051381:Rats; D013055:Spectrophotometry, Infrared
D008901:Mineralocorticoids; D000450:Aldosterone; C027514:19-noraldosterone