STEROIDAL CYCLIC KETALS. III.^{1, 2} HYDROCORTISONE AND RELATED CORTICOIDS

Abstract

The purpose of this paper is to describe the preparation of hydrocortisone3 (XIV), 11-epi-hydrocortisone (XV), and Reichstein's Substance E diacetate (V) from cortisone4 (VII), or its acetate (111), by an essentially new and facile method which entails the protection of carbonyl groups as ethylene k e t a l~.~ In this connection, Wendler, Huang-Minlon, and Tishler (1) have selectively protected the C-3, and -20 carbonyl groups of cortisone (VII) by semicarbazone formation. Moreover, these investigators demonstrated that cortisone acetate (111) formed only a 3-mono-semicarbazone. This revealed that the C-21 acetate group hindered the condensation reaction a t the neighboring (2-20 position. This steric effect has been noted previously by Mancera (2). Lithium borohydride reduction of cortisone-3,20-di-semicarbazone, followed by acetylation, and hydrolysis of the semicarbazone groupings (exchange reaction with pyruvic acid) afforded hydrocortisone acetate (XVI).Reichstein's Substance S acetate (I) (Flowsheet I) on treatment with excess ethylene glycol (benzene, p-toluenesulfonic acid) afforded a mono-ethylene ketal to which the structure I1 has been assigned. The product exhibited no selective absorption in the ultraviolet region of the spectrum. The coincident rearrangement of the double bond from the C-4 to the -5 position during the formation of ethylene ketals of A4-3-ketosteroids has been discussed previously (3). It is to be noted that here also the C-21 acetate group hindered the condensation of the C-20 carbonyl group with ethylene glycol. Similarly, only a 3-mono-ethylene ketal (IV) was obtained from cortisone acetate (111) (64% yield). However, and Rosenkranz, Pataki, and Djerassi (7b). (This last publication appeared after completion of our work.) 70An lla-hydroxyl group (in contrast to the 118-isomer) is capable of acetylation, as shown by Long and Gallagher, J .

Steroidal Cyclic Ketals. V. Transformation Products of Adrenosterone. The Synthesis of related C19O3-Steroids

“…The optical rotations conform to the generalization recently established for correlating the rotations of 11-oxygenated steroids (11,17); i.e., for a group of corresponding 11-oxygenated steroids the order of decreasing positive rotation…”

“…This may be ascribed to the over-all size of the, e.g., aluminum hydride ion, the species participating in the nucleophilic reduction (10). However, this laboratory has recently reported (11) an example in which this type of reduction elaborated simultaneously the 1 -hydroxy-compound in very low yield. It appears that frontal attack ma.y be possible to a very minor extent.…”

“…will be: 11 keto > 113-hydroxy > 1 -hydroxy (Table I). The ketals listed conform to this generalization, which observation is in contrast to our previous experience with these derivatives (11).…”

Struktur der Drevogenine. Glykoside und Aglykone, 267. Mitteilung.

“…Ferner ist iiberall ein Vinylproton (6-HI) bei 6 = ca. Drevogenin P 11, 13) Die genaue T,age dieses Maximums in Alkohol ist u. a. von der Substitution an C-11 abhangig [37] [38] (obersicht: [39] Spektrum von Di-0-acetyl-drevogenin P 12 (Fig. 14): Dort ist bei 6 = ca.…”

A Convenient Syntheses of 9(11)-Dehydrosteroids from 11β-Hydroxysteroids

“…70-75% .5 In the attempts to ketalize its epimer--1 ID-hydroxy androstenedione (1) under similar conditions, only 17-keto was found ketalized. Increased TsOH amount and prolonged period of 'To whom the correspondence should be addressed.…”