Dieter Bittler

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.

Synthese von pentacyclischen 7β,15β-ethano-steroiden

Abstract The synthesis of pentacyclic 7β,15β-ethano-androstene derivatives by intramolecular opening of a 15β,16β-methylene-17-oxo moiety with a 7β-malonyl ester function is described.

Säure-katalysierte umlagerungen on 15β,16β-methylen-17α-pregnen-21,17-carbolacton-derivaten

Zusammenfassung The different acid catalyzed rearrangements of 15,16-substituted 17α-pregnene-21,17-carbolactone derivatives are described.

A carbenoid route to C(1)–C(11) bridged steroids

Abstract The exocyclic olefin 3 enters into stereoselective cyclopropanations with dihalocarbenes on the steroid β-face to afford the protected spiro[2.5]octane analogues 4 and 5 . These intermediates are transformed into novel, highly strained steroid derivatives, like 9 , by utilizing an intramolecular cyclopropylidene insertion reaction en route to pentacyclic, C(1)–C(11) ethano-bridged steroids 13–20 .

18-Methyl-15α, 16α-Methylen-17α-Äthinyl-19-Nor-Testosteron

The synthesis and biological activities of 18-methyl-15α, 16α-methylene-17α-ethinyl-19-nortestosterone6 a are described.