Steroids. LXXIX. Synthesis and reactions of oxiranes obtained from 3- and 16-oxo steroids

Abstract

The synthesis of oxiranes from 3-and 17-keto steroids is described. Dimethylsulfonium methylide (1) reacted with estrone in a highly stereoselective manner by aside addition of CH2. or-Side addition also predominated in the reaction of 1 with 3-keto-5or steroids (although an earlier claim of stereospecificity has to be modified to stereoselectivity), whereas dimethyloxosulfonium methylide (2) gave products resulting from p-side attack on the 3-keto group. Stereochemistry of the products was demonstrated by chemical conversions. The oxiranes reacted with amines to yield amino alcohols. Spiro-17p-oxiranylestra-1,3,5( lO)-trien-3-01 (4a) reacted with sodium cyanide a t steam-bath temperature to yield 17a-cyanomethyl-3,17p-estradiol (Se), but under more strenuous conditions the product of this reaction was estrone.

Steroids and Steroidases. XIV. Studies on the Reactions of 2-Lithio-1,3-dithianes with Steroids Possessing Spiroepoxide Functions at C-32

“…Spiro-3a-oxiranyl-5a-androsran-I 7j-01 (1 1) and Spiro-3~-oxiranyI-5a-androsran-l7~-ol (1 2) 5a-Androstan-l7/l-ol-3-one and dimethylsulfonium rnethylide were reacted as described by Cook er al. (2) to give, after p.1.c. purification, a 90% yield of a mixture of the spiroepoxides 11, n.m.r.…”

“…Although pure samples of 1 and 5 had not been obtained by this method in the previous work (2), it was found that separation of the two epimers could be effected by careful preparative layer chromatography (p.1.c.). The supply of the 3a-oxide 1 was augmented by its preparation in 80"/,ield from the 5a-cholestan-3-one-dimethylsulfoxonium methylide reaction (2) and in view of the more ready availability of the latter oxide, the initial experiments were carried out on the sequence of reactions involving compounds the hydroxydithianyl compound 2 in 85% yield.…”

Steroids and Steroidases. XI. Synthetic Approaches to C-17 Bis(2-hydroxyethyl)-amino Compounds as Potential Precursors of 17-Hydroxyandrostane Nitrogen Mustards

“…The 17P-configuration of the epoxide group was verified by reduction of 13 with lithium aluminum hydride to 1 7~-methyl-5a-androstan-17P-01 (14, 70% yield) which showed peaks in the p.m.r. spectrum for the C-17 proton, and C-18 and -1 9 methyl groups at chemical shifts characteristic of 17P-hydroxy17cl-methyl steroids (13,14) and which was identical in all respects with an authentic sample prepared unamhiguously from 17~-methyltestos6That a single C-17 epimer only was formed was confirmed by the p.m.r. spectrum which showed the C-18 methyl protons as a sharp singlet at 6 0.86 p.p.m.…”

“…Dry dimethyl sulfoxide (10 ml) was added and the mixture was stirred for 45 min at 70' under nitrogen. Tetrahydrofuran (10 ml) was then added, the mixture cooled to -5", and solution of trimethylsulfonium iodide (30 g, 14.6 mmol) in dimethyl sulfoxide (23 ml) added rapidly with stirring (13). During this addition the reaction mixture solidified and the addition of further tetrahydrofuran (141111) became necessary.…”

“…A solution of spiro-17P-oxiranyl-5a-androstane (13,125 mg, 0.44 mmol) in morpholine (5 ml) containing phenol (55 mg) was refluxed for 24 h. The solution was then poured into water (25 ml) and extracted with ether (3 x 20 ml). The combined ether extracts were washed with aqueous sodium hydroxide (lo%, 3 x 10 ml), then with water (2 x 15 ml), and dried (MgSO4).…”