Aldosterone antagonists. 2. New 7.alpha.-(acetylthio)-15,16-methylene spirolactones

Abstract

Some 15,16-methylene derivatives of the aldosterone antagonist spironolactone were synthesized with the purpose of increasing the antialdosterone potency and reducing the endocrinological effects of this standard compound. By introduction of a 1,2-double bond and a 15 beta,16 beta-methylene ring in the spironolactone molecule both goals were achieved. In animal studies mespirenone exhibited a threefold-greater antialdosterone potency and less than 10% of the antiandrogenic activity of spironolactone.

Steroids: reactions and partial syntheses

“…The action of dichloroethyl phosphate upon 3a-acetoxy-12a-hydroxy-5~-cholanic acid in dichloromethane in the presence of triethylamine gives the bislactone (256) containing a sixteen-membered ring. 161 Hydrolysis of this diacetate with base gives the diol (257), the structure of which has been determined by X-ray analysis. Catalytic hydrogenation of the ester (258), prepared from lithocholic acid, has been studied under a wide variety of conditions.162 Hydrogenation in acetic acid over platinum leads to the Sa-dihydro derivative, without affecting the A8 bond of Ianosterol, thereby overcoming a major obstacle to the conversion of bile acids into tetracyclic triterpene antibiotics.…”

Bioinspired Divergent Synthesis of Aspersteroids A and B

“…Interestingly, treatment of 18 with singlet oxygen triggered a Schenck ene reaction/Schenck rearrangement cascade to generate C9 hydroperoxide 19a , which was reduced in situ with PPh 3 to furnish 20 in 65% yield. Reduction of 20 with lithium aluminum hydride, followed by regioselective oxidation of the C3 hydroxyl group with pyridinium chlorochromate, triggered simultaneous dehydration of the C5 hydroxyl group, which gave rise to aspersteroid B ( 2 ).…”

Synthesis of new 11.beta.-substituted spirolactone derivatives. Relationship with affinity for mineralocorticoid and glucocorticoid receptors

“…Several A or D ring substituted steroidal 7a-alkoxycarbonyl spirolactones have recently been synthesized leading to a reduction in the affinity for the androgen (AR) and progesterone (PR) receptors, whereas the mineralocorticoid activity was maintained at a high level. 2 The binding characteristics of these molecules for the MR were not described. On the other hand, some 11,12-dehydropregnane derivatives were found to exhibit high affinities for the MR,6 but displayed agonistic rather than antagonistic activities.…”