The Structure and Function of Oestrogens. IX Synthesis of the trans Isomer of 5,5,10b-Trimethyl-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol

Article abstract of DOI:10.1071/CH9880735

Alkylation of ketene methyl trimethylsilyl acetal (10) with 1ξ-acetoxy-6-methoxy-2-(p-methoxyphenyl)-2-methyl-1,2,3,4-tetrahydronaphthalene (9) in the presence of zinc iodide gave 84percent of methyl (1'RS,2'RS)-2-<6'-methoxy-2'-(p-methoxyphenyl)-2'-methyl-1',2',3',4'-tetrahydronaphthalen-1'-yl>ethanoate (11a).Cyclization of the derived acid (11b) with methanesulfonic acid gave 89percent of 2,8-dimethoxy-10b-methyl-cis-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (12a), Clemmensen reduction of which afforded 52percent of 2,8-dimethoxy-4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene (12b).Oxidation of (12b) with dichlorodicyanobenzoquinone gave 70percent of the conjugated enone (4), which upon hydrogenation over 10percent palladium/charcoal gave a 5:1 ratio of 2,8-dimethoxy-10b-methyl-trans-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (14) and the cis isomer (12a).Exhaustive methylation of the trans ketone (14) yielded 49percent of 2,8-dimethoxy-5,5,10b-trimethyl-trans-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (16), which upon Clemmensen reduction followed by O-demethylation afforded 5,5,10b-trimethyl-trans-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol (2).