Karl Petzoldt

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.

Microbial hydroxylations of β-carboline derivatives

Ethyl β-carboline-3-carboxylate (1a) and its 4-alkyl derivatives (1b–d) are hydroxylated by Sporotrichum sulfurescens at C-6 and C-8 of the aromatic nucleus; side chain hydroxylation of (1c) and (1d) occurs with Streptomyces lavendulae and Streptomyces griseus.

Synthese von 11β,21-dihydroxy-6α,16α-dimethyl-1,4-pregnadien-3,20-dion und seines 9-fluor-derivates

Abstract 6β,16α-Dimethyl-5α-pregnane-3β,5,20,21-tetrol (6a) prepared from 3β-hydroxy-21-acetoxy-16α-methyl-5-pregnene-20-one (1) is oxidized microbiologically only to the 3-keto-compound 7. The desired 21-hydroxy-6α,1,16α-dimethyl-4-pregnene-3,20-dione (10) was formed by chemical oxidation and known reactions. It was hydroxylated microbiologically to the corticosterone compound 12a, which also was obtained by hydroxylation of the corresponding 6β-methyl structure with subsequent acidic isomerization. The microbiological dehydrogenation yields the 11β, 21-dihydroxy-6α,16α-dimethyl-1,4-pregnadiene-3,20-dione (13a). The analogous 11α-hydroxy compound 16, which was transformed to the 9-fluor-11β,21-dihydroxy-6α,16α-dimethyl-1,4-pregnadiene-3,20-dione (22), was prepared by microbiological 11α-hydroxylation and l-dehydrogenation in a kind of mix-fermentation.

Product stereospecificity in the microbial reduction of imidazol-1-yl methyl aryl ketones

Abstract Various microorganisms can be used to reduce ketoimidazole 3 to hydroxyimidazole 4. Only one enantiomer (i.e., (R)-4) is produced. In contrast, ketoimidazolium salt 2 is not reduced under identical conditions.

Untersuchungen zur Steroidhydroxylierung und Systematik von Pilzen der Deuteromycetengattungen bei Curvularia und Helminthosporium

Summary1.A method for the selective isolation of Curvularia and Helminthosporium is described.2.29 strains of Curvularia lunata, 32 strains of 24 different Curvularia species, and 18 Helminthosporium strains are tested for their ability to saponify 6 α-Fluor-21-acetoxy-16α-methyl-4-pregnene-3,20-dione (FMDOCA) and to hydroxylate the free compound FMDOC and compound Reichstein S in the 7α,9α,11β und 14α position.3.Almost all strains were able to saponify FMDOCA.4.Only few strains of Curvularia lunata and two strains of Helminthosporium were able to hydroxylate compound RS or FMDOC in 11β position at interesting quantities.5.In systematics and morphology no correlations with the physiologic abilities of these strains could be detected.Zusammenfassung1.Eine Methode zur selektiven Isolierung von Curvularien und Helminthosporien wird beschrieben.2.29 Stämme von Curvularia lunata, 32 Stämme von 24 verschiedenen Curvularia-Arten und 18 Stämme von verschiedenen Helminthosporium-Arten wurden auf ihre Fähigkeit 6α-Fluor-21-acetoxy-16α-methyl-4-pregnen-3,20-dion (FMDOCA) zu verseifen und Reichstein-Substanz-S und FMDOC in 7α,9α11β und 14α Stellung zu hydroxylieren, untersucht.3.Fast alle untersuchten Stämme können FMDOCA gut verseifen.4.Zur 11β-Hydroxylierung mit hoher Ausbeute sind nur einige Stämme von Curvularia lunata und zwei Helminthosporium-Stämme befähigt.5.In der Systematik und Morphologie ließen sich keine Parallelen zu den physiologischen Fähigkeiten dieser Stämme aufzeigen.

A Microbiological approach to kinetic resolution of racemic estra-4,9-dienes

Abstract Resolution of rac.-estra-4,9-diene-3,17-dione is achieved by enantioselective, microbiological reduction.