Ch. Meystre

Neue Substitutionsreaktionen bei Steroiden

The intramolecular substitution of the angular methyl groups in steroids by attack of O-radicals derived from 6β-, 11β, and 20-alcohols is discussed. Irrespective of their genesis, these radicals abstract a hydrogen atom from one of the said methyl groups, suitably oriented inδ-position. The C-radicals thus formed give different products depending on the neighbouring groups. It is shown that 20-hydroxy-18-C-radicals combine with iodine atoms, to give 18-iodides which can befurther substituted through radicals to give potential 18-oxo-compounds in high yield. In the case of 20-cyanohydrines, the intramolecular reaction of the 18-C-radical with the cyano groups gives rise to the new 18-cyano-20-oxo-steroids. With 6β- and 11β-O-radicalssingle substitution in 19-position predominates, since the steric arrangement of the primary product favours the intramolecular ether formation over a second substitution reaction. A general reaction scheme for these transformations is proposed.

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.

Partialsynthese des Aldosterons

The preparation of the (18 → 11β)-lactone ofΔ 5-3-ethylenedioxy-11β-hydroxy-21-acetoxy-20-oxo-pregnen-18-oic acid (XV) is reported. Since this compound has previously been transformed into aldosterone, the reactions described represent the first partial synthesis of this important hormone from readily available 18-unsubstituted natural steroids.

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.

Einwirkung von N-Brom-succinimid aufΔ4-3-Keto-steroide

The bromination ofΔ 4-3-keto-steroids with the aid of N-bromo-succinimide takes place in 6-position, that is in allyl-position and not inα-position to the keto group. By splitting off hydrogen bromide from these 6-bromo-compounds,Δ 4;6-3-keto-steroids are obtained in known manner.

Seitenkettenabbau von Gallensäuren direkt zu Ketolen vom Typus der Nebennierenrinden-Hormone

δ20;23-24, 24-Diphenyl-choladienes are easily brominated in 21-position by N-bromo-succinimide. The bromo-dienes obtained can be transformed into 21-hydroxy-, 21-acyloxy- or 21-alkoxy-dienes and the latter two split by oxidation into 21-acyloxy- or 21-alkoxypregnane-20-ones. This sequence of reactions, of which the last two may be exchanged, affords a new and simple degradation method, leading from bile acids directly to ketols of the type of the suprarenal cortical hormones.