The Structure and Function of Oestrogens. II. The Synthesis and Oestrogenic Activity of 4b-Methyl 4b,5,6,12-tetrahydrochrysene-2,8-diol and 4b-Methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol and Related Compounds

Abstract

Hydroboration of an inseparable mixture of 2,8-dimethoxy-5,6-dihydrochrysene (5a) and 2,8-dimethoxy-4b-methyl-4b,5,6,12-tetrahydrochrysene (6a) followed by oxidation with alkaline hydrogen peroxide gave a mixture of (4bα,10bβ,11β)-2,8-dimethoxy-4b-methyl-4b,5,6,10a,11,12-hexahydrochrysen-11-ol (10a) and its (4bβ,10bβ,11β) isomer(11a). Reduction of the methanesulfonate ester of (10a) with lithium aluminium hydride in ether gave 2,8-dimethoxy-4b-methyl-trans-4b,5,6,10b,11,12- hexahydrochrysene (2b), identical with material prepared by another route. Reduction of the methanesulfonate of (4bβ,10bβ,l1β)-2,8-dimethoxy-4b-methyl-4b,5,6,10a,11,12-hexahydrochrysen- 11-ol afforded 2,8-dimethoxy-4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene (12), demethylation of which afforded 4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol (14b). Dehydration of the mixture of the 11-epimeric alcohols (10a) and (lla) with phosphorus oxytrichloride in pyridine yielded pure 2,8-dimethoxy-4b-methyl-4b,5,6,12-tetrahydrochrysene (6a) which was demethylated with methylmagnesium iodide to give the corresponding dihydroxy compound (9). Other compounds prepared in the course of examining possible routes to (9) and (14b) include 13,13-dichloro-2,8-dimethoxy-4b,5,6,10b,11,12-hexahydro-4b,10b-methanoch rysene (3a), 1-bromo- 2,8-dimethoxy-5,6-dihydrochrysene (5b), and 11-bromo-2,8-dimethoxy-4b-methy1-4b,5,6,12-tetra- hydrochrysene (7). The oestrogenic activities of some of the new angularly methylated hydrochrysenes and of 9α- methyloestradiol (15) are reported.