The C-16 Halides of Estrone Methyl Ester

Abstract

Epimeric forms of four C-16 halides of estrone methyl ether are reported. Chemical reactions are presented which include proof of structure, isomerization, interconversion and reduction. Two C-17 halides of 16-estrone methyl ether are similarly discussed.Noteworthy and often valuable alterations of clinical activity accompany the exchange of halogen for hydrogen at various points in the steroid nucleus. Progestational, cortical, and androgenicanabolic steroids have received most attention in structure-activity studies.1 Our interest in halogenated estrone derivatives was prompted by the possibility that we could retain the favorable

Hypoiodite Oxidation of 3α-Bromo and 3α-Chloro-2β-Hydroxy-5α-Androstan-17-one

“…Both iodoketones (IV and V) showed carbonyl maxima at 1725 cm.-', the same as for the noniodinated product (111). A similar observation was made by Mueller and Johns in the estrone series (6). These results emphasize the hazards in attempting to translate relationships established in the cyclohexanone series to substituted cydopentanones.…”

“…The structural assignments for the epirneric iodoketoncs (IV and V) wcre based on chemical evidence as well as spectral and elemental analysis. The 16a-epimer (V) was synthesized by first COIIverting 111 to its enol acetate (IX) followed by iodination with iodine and mercuric acetate as described by Mueller and Johns (6). NO 16pisonier (IV) was isolated in this experiment…”

Dichlororuthenium(IV) Complex of meso‐Tetrakis(2,6‐dichlorophenyl)porphyrin: Active and Robust Catalyst for Highly Selective Oxidation of Arenes, Unsaturated Steroids, and Electron‐Deficient Alkenes by Using 2,6‐Dichloropyridine N‐Oxide

“…These epoxides are usually prepared through stoichiometric reactions that either give low to moderate diastereoselectivity or require tedious experimental procedures. For example, the C17‐epoxides of estrone and its derivatives (which have potential uses in oral contraceptive treatment of hyperandrogenism and in the treatment of hormone‐dependent breast cancer in postmenopausal women55) can be obtained by oxidation using m ‐CPBA with a diastereoselectivity of α/β=80:20,55a, 56a,56c by ring closure of trans ‐bromohydrin with strong inorganic base,56c,e and by reaction of the carbonyl group (C17) at D ring with sulfur ylide (Me 3 SOI/KO t Bu) 55c–. However, there are few reports on the synthesis of the C17‐epoxides of unsaturated steroids through catalytic processes 10d.…”

Synthesis of Dehydroepiandrosterone Sulfatide and 16α-Halogenated Steroids

“…The fact that a-subtitution at the C-16-pOsition enhancea biological activity of certain steroids, coupled with the intention to fmd more potent and stable compounds, led to the preparation of 16a-halo derivatives of epiandrosterone (8)(9)(10). 16a-Chloro, bromo, and fluoro derivatives were prepared from epiandrosterone according to reaction sequence shown in Scheme 111.…”