Alan J. Solo

Ring-D-bridged steroid analogs. VI. Proof of stereochemistry and further reactions of 14α, 17α-etheno-16α-carbomethoxypregn-5-ene-3β-ol-20-one acetate

Abstract Curtius degradation of 14α, 17α-etheno-16α-carboxypregn-5-ene-3β-ol-20-one acetate (IV) to the benzylurethane (V) is described. Selective catalytic reduction of 14α, 17α-etheno-16α-carbomethoxypregn-5-ene-3β-ol-20-one acetate (III) afforded 14α, 17α-ethano-16α-carbomethoxypregn-5-ene-3β-ol-20-one acetate (VI). Hunsdiecker degradation of the carboxylic acid VIII, derived from VI gave 14α, 17α-ethano-16α-iodopregn-5-ene-3β-ol-20-one acetate (IX). Hydrolysis of IX to the 3β-alcohol X was followed by catalytic reduction to 14α, 17α-ethano-5α-pregnane-3β-ol-20-one (XI). The latter compound was also prepared from 14α, 17α-ethenopregn-5-ene-3β-ol-20-one (XII). The stereochemistry previously assigned to I, on the basis of analogies, has been proved by a combination of chemical and physical evidence, including an x-ray crystal structure determination on IX.

Agents for alkylating steroid hormone receptors. I. Analogs derived from esters of 17α-hydroxyprogesterone

Abstract A method designed to selectively tag hormonal receptor sites is discussed. Acylation of 17 α -hydroxyprogesterone with the half acids, half esters of glutaric, adipic, and pimelic acids followed by selective hydrolyses afforded the ω -carboxybutanoate, the ω -carboxypentanoate, and the ω -carboxyhexanoate of 17 α -hydroxyprogesterone. These acids were converted via their acid chlorides to the 5-keto-6-diazohexanoate, the 6-keto-7-diazoheptanoate, and the 7-keto-8-diazooctanoate of 17 α -hydroxyprogesterone. The latter compounds were active in the Clauberg assay, but they appear not to have alkylated the Clauberg receptor.

Ring-D-bridged steroid analogs. VII. Homoconjugate Diels-Alder addition of methyl propiolate to substituted bicyclo [2.2.1] heptadienes.

Abstract 3β-Acetoxy-20-keto-5,14,16-pregnatriene (I) reacts with hexafluorobutyne or with dimethyl acetylenedicarboxylate to form normal Diels-Alder adducts. However, reaction of I with methyl propiolate leads to the stereospecific formation both of normal Diels-Alder adduct and of a diadduct derived from homoconjugate addition of a second mole of dienophile to the monoadduct. The stereochemistry of the monoadduct was established by a correlation with 14α, 17α-ethano-16α-carbomethoxypregn-5-ene- 3β-ol-20-one acetate. The homoconjugate addition of methyl propiolate to methyl bicyclo [2.2.1]heptadiene-2-carboxylate is alsodescribed.

Ring-d-bridged steroid analogs. IX. 19-nor-14α, 17α-ethano-16α-carbomethoxy-4-pregnene-3, 20-dione.☆

Abstract The synthesis of 19-nor-14α, 17α-ethano-16α-carbomethoxypregn-4-ene-3,20-dione (X) from 3β-acetoxy-14α, 17α-ethano-16α-carbomethoxy-pregn-5-ene-20-one (III) is described. In the Clauberg Assay (subcutaneous administration), 16α-carbomethoxypregn-4-ene-3,20-dione has been found to have approximately 3.5% the activity of progesterone. Introduction of a 14α, 17α-ethano bridge further reduces the activity by more than a factor of 4. In contrast to this, the 19-nor compound (X) appears to be at least 167% as active as progesterone and over 25X as active as 14α,17α-ethano-16α-carbotnethoxypregn-4-ene-3,20-dione (XII). The significance of these facts with respect to the possible mode of progesterone binding to the Clauberg receptor is discussed.