METHOD OF SYNTHESIS OF γ-LACTONE 3 OF (7α-ACETYLTHIO-17β-HYDROXY-3-OXOANDROST-4-ENE-17α-YL)-PROPIONIC ACID Russian patent published in 2001 - IPC

FIELD: organic chemistry, chemical technology, pharmaceutical chemistry. SUBSTANCE: invention relates to the improved method of synthesis of potassium-preserving diuretic, namely, spironolactone (verospiron, aldactone) from available raw - sterols of vegetable and animal origin. Spironolactone [γ-lactone 3 of (7α-acetylthio-17β-hydroxy-3-oxoandrost-4-ene-17α-yl)-propionic acid] of the formula (I): γ is synthesized from androstendione or its derivative of the formula (II): 7α where 17β means carbonitrile; 17α means hydroxyl that is subjected for protection with -3-ketosystem, methylenation at 17-keto-group with dialkylsulfonium methylide generated in situ from trialkylsulfonium halogenide followed by conversion of synthesized oxirane cycle to lactone cycle by formation of -dienone structure, addition of thioacetic acid and isolation of the end product. Formation of R¹-dienone system is carried out after preliminary formation of lactone ring and simultaneous decarboalkylation by heating in aprotonic solvent in the presence of catalytic amount of saturated aqueous solutions of salts of strong bases and strong acids, selective functionalization of 6th position of steroid molecule using haloidation-dehydrohaloidation reactions. Then thioacetic acid is joined and the end product is isolated. Method ensures to avoid the formation of by-side products and resinification of reaction mass as result of carrying out reaction under mild conditions. EFFECT: improved method of synthesis, increased yield of main product. 9 cl, 12 ex