Rudolf Wiechert

New steroids with antiprogestational and antiglucocorticoid activities

A number of 11-substituted 19-norsteroids with inverse configuration at C-13 were synthesized. 11 beta-Aryl compounds in this series were found to possess antiprogestational and antiglucocorticoid activities.

Reductive desulfonylation of phenyl sulfones by samarium(II) iodide-hexamethylphosphoric triamide

Abstract Samarium(II) iodide in tetrahydrofuran reductively desulfonylates phenyl sulfones in the presence of hexamethylphosphoric triamide. This transformation is illustrated here for ten substrates, which include secondary alicyclic, β-hydroxy, vicinal bis-, and α,β-unsaturated sulfones.

Synthesis and pharmacological evaluation of 8α-estradiol derivatives

Abstract A number of 2- and 16-alkyl 8α-estradiol derivatives were synthesized and pharmacologically characterized with respect to estrogenic/antiestrogenic activities.

Synthesis of antiprogestational steroids.

The discovery of the first competitive progesterone antagonist RU 38,486 has initiated an intense search for more potent and more selective anti-progestins. Among several hundreds of compounds under preliminary investigation, biological characterization is most advanced for derivatives RU 38,486, ZK 98,734 and ZK 98,299. These compounds do not only differ in relative potency, but are clearly distinguished by their different behaviour in various animal models. Emphasis is laid on the synthetic problems associated with chemical operations in a sterically crowded environment as represented by structures RU 38,486 and ZK 98,299.

New biologically active pregnan-21-oic acid esters

Abstract Among the metabolites of fluocortolone (IV), isolated from human urine, there was found fluocortolone-21-acid (XI). This metabolite and several ester derivatives were synthesized by different routes starting from fluocortolone. The synthetic methods used to prepare the fluocortolone acid esters were extended to other corticoid derivatives. Several pregnan-21-oic acid esters possess the unique activity that they are topical anti-inflammatory agents with no side effects. Even when administered at high dosages, the usual systemic activity associated with corticosteroid treatment could not be observed.

Synthetic variations of the progesterone antagonist RU 38 486

Abstract Irradiation of 17-keto-estranes bearing an 11-aryl substituent offers a preparatively useful access to pharmacologically interesting steroids with inverted configuration at C-13.

Stereoselective epoxidation of 5(10),9(11)-estradienes

Abstract 3,3-(2,2-Dimethyltrimethylene-1,3-dioxy)-5(10),9(11)-estradien- 17-one is converted to its 5α,10α-epoxide by iron phthalocyanine/iodosylbenzene in a highly stereoselective manner.

Synthesis and activities of anti-aldosterones

Publisher Summary This chapter discusses the synthesis and activities of anti-aldosterones. An aldosterone antagonist can prevent or decrease edema formation by competitively inhibiting aldosterone at the receptor level. The antagonist functions as a diuretic agent and causes decreased blood pressure. In a study described in the chapter, the anti-aldosterone activity of a bis-methylene derivative was compared to that of spironolactone by a method involving a continuous i.v. infusion of aldosterone in rats and in man. In this study, adrenalectomized rats were pretreated with fluocortolone caproate and fluocortolone. Five days after adrenalectomy, these rats received a continuous infusion of aldosterone. Spironolactone and a bis-methylene derivative were given orally l h before beginning aldosterone infusion. Urine production, volume and electrolyte concentration were measured hourly. The bis-methylene derivative was found to reverse the strong depression of the urinary Na/K ratio induced by the mineralocorticoid effect of aldosterone in a dose-dependent manner and had more than five times the potency of spironolactone. A study with healthy human subjects also confirmed this result.

Configuration and conformation of the A-ring of 1-methyl steroids.

Abstract A detailed NMR analysis of epimeric pairs of 1-methylated steroids in the A/B cis and Δ4-series has confirmed earlier configurational assignments. One-methyl steroids in the A/B trans series and the 1-methyl hydrocortisone synthesized therefrom are revised from the α to β-configuration. One-β-methyl-5α and 1β-methyl-Δ4 steroids were judged to be distorted from the normal chair-formed A-ring conformation, the former into the twist and the latter into the alternative half-chair form.

Synthesis of ENT-17-(prop-1-ynyl-17β-hydroxy-11β-(4-(N,N-dimethylamino) -phenyl)-4,9-estradien-3-one, the antipode of RU — 38 486

The title compound was synthesized and tested for its biological activities. It showed neither antiprogesterone nor antiglucocorticoid properties.