INVESTIGATIONS ON STEROIDS. VI. NEW METHOD OF PREPARING 6(α)-ACETOXYPROGESTERONE¹

Abstract

In an earlier publication (1) a procedure was described for the preparation of certain steroids which are substituted at carbon atom 6 by an acetoxyl group. The arrangement in ring A of these compounds was the same as in the most active hormones of the androstane and pregnane series. Hence carbon atom 3 existed as carbonyl carbon and there was a double bond between carbon atoms 4 and 5. The examples given were the preparation of 6(a)-acetoxyandrostenedione and of 6(a)-acetoxydesoxycorticosterone. It was pointed out that 6(a) -acetoxyprogesterone (VI) previously obtained by Ehrenstein and Stevens (2) according to another procedure should also be accessible by means of the new scheme. The present investigation demonstrates that this is actually the case and that the new method is preferable to the old one.Starting material for this sequence of reactions was 5-pregnene-20-one-3(/3)-ol (I). Treatment of this substance with perbenzoic acid yielded mainly (65%) the (5,6)(a)-oxide (II) as was shown by the subsequent reactions. It was pointed out in the earlier paper (1) that (5,6) (a)-oxides furnish with glacial acetic acid 6-acetoxy compounds, whereas (5,6)(dioxides yield 5-acetoxy compounds. When pregnane-(5,6)(a)-oxide-20one-3(/3)-ol (II) was treated with glacial acetic acid under proper experimental conditions, only a small quantity of the by-product, pregnane-20one-3(j3), 5,6(¿rans)-triol 3,6-diacetate (IV), resulted. The main product (61.3%) of the reaction was pregnane-2O-one-3(0) ,5,6(trans)-triol 6monoacetate (III). Acetylation of this compound with acetic anhydride yielded the above mentioned 3,6-diacetate (IV).We had previously prepared (2) the 6-monoacetate (III) by partial hydrolysis of the 3,6-diacetate (IV). For the 6-monoacetate (III) the melting point 222-226°was observed. The melting point of the same compound obtained by acetolysis of the (5,6)(a)-oxide (II), however, was 1 Aided by a grant from the Smith, Kline, and French Laboratories in Philadelphia.Read before the Division of Organic Chemistry at the St. Louis meeting of the

STEROIDS. XIV.1 STUDIES IN THE 3,6-DIHYDROXYPREGNANE SERIES (PART I)

“…Recrystallization from methanol-chloroform raised the m.p. to 252-255°, [a]" +58.8°[ reported (5,13) m.p. 256-258°].…”

“…Crystallization from hexane-acetone gave 10.66 g. (68%), m.p. 164-170°, which was raised on further recrystallization to 173-175°, [«]" +5°( acetone) [reported (4) m.p. 175.5-176°, [a]D +3.5°(acetone)].…”

“…Soc., 677 (1938)]. 4 Desoxytigogenin is known (8), but its degradation does not seem to have been carried out. The present specimen of desoxytigogenin was prepared by a new method (9).…”

Investigations on steroids. XX. 6β- and 6α-Acetoxy- and Hrdroxy-Derivatives of Progesterone and Androstenedione

“…On repeating the experiment in "redistilled dried chloroform," an amorphous a, /3-unsaturated ketone of the same composition was obtained which resisted all attempts at crystallization. It was considered an "amorphous modification" of the same compound (8). That the slight difference in the solvent would account for this discrepancy, was not evident at that time.…”

The Chemistry of the Steroids

“…The �-oxide (VII) should be called hydroxy-5 :6( <x)-oxidocholestane.� The arbitrary current nomencla ture is thus shown to be correct. By comparing the typical differences of the specific rotations established space formulae may be assigned to the other known oxides of·the same type, e.g., the 5: 6-oxides of dl) androstene-3 (� ) -01-17 -one (23) , A 5-pregnene-3 (� ) -01-20-one (24) , and A5-pregnene-3(�),21-diol-20-one (2S).…”