ChemInform Abstract: STEROIDS. XLIV. PROTON NMR STUDIES. CONFIGURATIONAL ASSIGNMENT OF 16,17‐DISUBSTITUTED STEROIDS

11.beta.-Substituted Estradiol Derivatives, Potential High-Affinity Carbon-11-Labeled Probes for the Estrogen Receptor: A Structure-Affinity Relationship Study

“…The direct oxidation of the metal enolate from ketones [10][11][12] reagents (such as oxaziridine15 or molybdenum perox-ide16) gave unsatisfactory results (incomplete reaction, impure product). However, oxidation of the 16a-position was more efficiently accomplished by a two-step procedure consisting of the conversion of protected ketones [10][11][12] into the corresponding enol phosphates 13-15 (reaction with lithium diisopropylamide and quenching with diethyl chlorophosphate) followed by a standard dihydroxylation procedure (M-methylmorpholine N-oxide and osmium tetraoxide), as reported for similar substrates.17 Because of their instability in the chromatographic purification, the mono-protected derivatives resulting from the above sequence were not isolated but directly deprotected to give hydroxyestrones [16][17][18]. Addition of 2-methoxypropene gave crude, fully protected hydroxyestrones 19-21, which underwent reaction with the appropriate organometallic reagent to give (after removal of the O-protecting groups) target compounds 2a-e, 4a-d, and 6a-e, respectively.…”

“…Compound 9 was obtained as reported.2*' 17 -Unsubstituted estradiol derivatives 4a and 6a were obtained from the corresponding 17-ketones by reduction with sodium borohydride. RBA data of compounds 3a,c and 5a were taken from the literature.2' General Conditions for the Conversion of Estrones (7-9) and 16a-Hydroxyestrones (16)(17)(18) to the Respective -Protected Derivatives (10)(11)(12)(19)(20)(21). A mixture containing the estrone derivative (10 mmol), picric acid (a few crystals), and 2-methoxypropene (10 mL; added after picric acid had been dissolved) in benzene (100 mL) was heated at 50 °C with rapid stirring in a stoppered flask until the starting material was completely consumed.…”