A. Wettstein

Isolierung eines neuen kristallisierten Hormons aus Nebennieren mit besonders hoher Wirksamkeit auf den Mineralstoffwechsel

A new crystalline compound has been isolated from beef adrenal extracts. In three different assay methods using epinephrectomised rats or dogs it was found to be from 30 to 100 times as potent as cortexone (11-deoxy-corticosterone) or its acetate.

Konstitution des Aldosterons, des neuen Mineralocorticoids

Chemical degradation of the new crystalline mineralocorticoid provisionally called electrocortin has shown that this compound is 11β, 21-dihydroxy-3, 20-diketo-4-pregnen-18-al. In solution this reacts mainly as the 11-hemiacetal. We suggest aldosterone as a definitive name for the compound.

Über eisenhaltige Wachstumsfaktoren, die Sideramine, und ihre Antagonisten, die eisenhaltigen Antibiotika Sideromycine

A new group of iron-containing metabolites, with growth stimulating properties for a number of microorganisms, has been isolated from streptomycetes and namedferrioxamines. It is proposed to include them, together with some known substances, like ferrichrome, coprogen and the terregens factor, which either contain or bind iron, in a new class of growth factors, thesideramines. The biological property of the sideramines is counteracted by iron-containing antibiotics from streptomycetes, thesideromycins. They comprise, besides known products like grisein and albomycin, two new groups of antibiotics, among them the highly potentferrimycins.

Über Synthesen in der Aldosteron-Reihe I. Totalsynthese des racemischen Aldosterons

d,l-Aldosterone (XXIV) has been prepared by total synthesis, involving more than 20 new steps, from the tricyclic compound I.

Biosynthèse des hormones stéroïdes

The different pathways of biosynthesis are described, by which steroid hormones are producedin vivo in the gonads, the adrenal cortex and the placenta, orin vitro by corresponding tissue preparations. First of all a short outline of the origin of cholesterol from acetyl coenzyme A through the ‘biological isoprene unit’, the pyrophosphate of Δ3-iso-pentenol, through squalene, lanosterol and zymosterol is given. Partial side-chain degradation of cholesterol, where ACTH plays an important role, leads to pregnenolone and further to progesterone. The latter compounds are the starting material for the other steroid hormones. On the one hand, they are converted in the gonads and adrenals into 17α-hydroxy derivatives, in which the side chain is completely removed by enzymes of the said and also of non-endocrine tissues, to form the androgens. Furthermore the adrenals produce their own typical androgens. After hydroxylation of the angular 19-methyl group, androgens are aromatised to estrogens. On the other hand, the adrenal converts progesterone by hydroxylation in 21- and, depending on the case, also in 11- and/or 17-position into the classical adrenocortical hormones. The special feature of an 18-hydroxylation and -dehydrogenation forms part of the biogenesis of aldosterone; a new example is given for the methods used towards its elucidation, consisting in the biosynthetic conversion of progesterone into two virtual intermediates, 18-oxo-progesterone and 21-desoxyaldosterone, which already contain the 18-aldehyde group, characteristic for aldosterone. The regulation of the biogenesis of the different hormones is mentioned and compounds are discussed which block one or other of the biosynthetic steps.The different pathways of biosynthesis are described, by which steroid hormones are producedin vivo in the gonads, the adrenal cortex and the placenta, orin vitro by corresponding tissue preparations. First of all a short outline of the origin of cholesterol from acetyl coenzyme A through the ‘biological isoprene unit’, the pyrophosphate of Δ3-iso-pentenol, through squalene, lanosterol and zymosterol is given. Partial side-chain degradation of cholesterol, where ACTH plays an important role, leads to pregnenolone and further to progesterone. The latter compounds are the starting material for the other steroid hormones. On the one hand, they are converted in the gonads and adrenals into 17α-hydroxy derivatives, in which the side chain is completely removed by enzymes of the said and also of non-endocrine tissues, to form the androgens. Furthermore the adrenals produce their own typical androgens. After hydroxylation of the angular 19-methyl group, androgens are aromatised to estrogens. On the other hand, the adrenal converts progesterone by hydroxylation in 21- and, depending on the case, also in 11- and/or 17-position into the classical adrenocortical hormones. The special feature of an 18-hydroxylation and -dehydrogenation forms part of the biogenesis of aldosterone; a new example is given for the methods used towards its elucidation, consisting in the biosynthetic conversion of progesterone into two virtual intermediates, 18-oxo-progesterone and 21-desoxyaldosterone, which already contain the 18-aldehyde group, characteristic for aldosterone. The regulation of the biogenesis of the different hormones is mentioned and compounds are discussed which block one or other of the biosynthetic steps.

Bildung von 17α-Hydroxy-Δ5-pregnenolon und 3β-Hydroxy-17-keto-Δ5-androsten (DHA) in Nebennieren- und Testes-Gewebe

The transformation of Δ5-pregnenolone into 17α-hydroxy-Δ5-pregnenolone, and of the latter into DHA, is shown to occur in homogenates and fractions thereof, both of bovine adrenal and testicular tissue. The relative significance of these reactions for the biogenesis of androgens in normal and neoplastic tissue is discussed.

Mikrobiologische Spaltung razemischer Steroide. Synthese vond-Aldosteron

A racemic intermediate in the total synthesis ofd, l-aldosterone, thed, l-20-oxo-pregnene derivative I, was converted by incubation with a mold hydroxylating in the 21-position into thed-20-oxo-21-hydroxy-pregnene derivative II, whereas thel-antipode of the starting material remained unchanged. This stereospecific microbiological reaction, comprising a separation of racemic modifications, represents the last remaining step in the synthesis of naturald-aldosterone. Other microbiological conversions of racemic steroids, dehydrogenation and hydrogenation, were also shown to proceed only with thed-enantiomer, leaving thel-form of thed, l-substrate intact. The advantages of this new microbiological method for the resolution of racemic modifications during the total synthesis of steroids are discussed.A racemic intermediate in the total synthesis ofd, l-aldosterone, thed, l-20-oxo-pregnene derivative I, was converted by incubation with a mold hydroxylating in the 21-position into thed-20-oxo-21-hydroxy-pregnene derivative II, whereas thel-antipode of the starting material remained unchanged. This stereospecific microbiological reaction, comprising a separation of racemic modifications, represents the last remaining step in the synthesis of naturald-aldosterone.

Ein neues Verfahren zur Herstellung von 19-Norsteroiden

The new methods for the production of 19-norsteroids described involve the conversion of 5α-halogen-6β-hydroxy-steroids into the corresponding 5α-halogen-6β:19-ethers either with lead tetraacetate or by the hypoiodite reaction8,10. The 6β:19-oxygen bridge is then opened reductively either directly or after oxidation of the 6β:19-ethers to lactones or preferably after introduction of a Δ4,6-3-oxo grouping. Acylolytic cleavage of the Δ4-3-oxo-6β:19-ethers followed by alkaline hydrolysis gives Δ4,6-3-oxo-19-hydroxy-steroids. The 19-hydroxycompounds formed are easily converted into 19-norsteroids by known methods.

Umwandlung von radioaktivem Cortexon in Aldosteron durch Nebennieren-Enzyme

Cortexone labeled in the 21-position with C14 yielded radioactive Aldosterone through incubation with beef adrenal homogenate. Its activity, due entirely to the 21 carbon atom, showed that about 48% of the Aldosterone had arisen from a direct conversion of cortexone without intermediate degradation. The low yield by weight in this conversion suggests, however, that cortexone is not the only natural precursor for Aldosterone in the adrenal. The radioactivity of the corticosterone obtained showed that about 84% of it originated from added cortexone. Lack of radioactivity of the hydrocortisone confirmed that it does not essentially result from cortexone.

Biologische Hydroxylierungen von Steroiden

New observations on the necessary cofactors for the hydroxylation of steroids using adrenal homogenates are described. By microbiological hydroxylation of steroids preferably in 11α-position using molds i. a. the new 11-epimers of corticosterone and 17-hydroxy-corticosterone have been obtained. They are lacking high mineralocorticoidal activity.