Antioestrogenic and antifertility compounds. III. Enantiomers of (±)-hexoestrol and its homologues

Abstract

(±)-2,3-Bis(p-hydroxyphenyl)butane (5a) and (&)-3,4-bis(p-hydroxyphenyl)-hexane (5c) were resolved, and absolute stereochemistry of the former was established as (-)-(2R,3R) by correlation with (+)-(R)-2,3-bis(p-methoxyphenyl)but-1-en. The (+) and (-) isomers of erythro-2,3-bis(p-hydroxyphenyl)pentane (Sb) were synthesized from (-)- and (+)-erythro-2,3-bis(p-methoxyphenyl)valeric acid, respectively. (+)-erythro-2,3-Bis(p-hydroxyphenyl)pentane (5b) was shown to have the (2R,3S) configuration, and (+)-threo-(b) the (2S,3S) configuration, by correlation with (-)-(8)-2,3-bis(p-methoxyphenyl)pent-1-ene. It follows that the configuration of erythro-2,3-bis(p-methoxyphenyl)-valeric and the corresponding-butyric acid is (+)-(2S,3R). Interaction of optically active hexoestrol and its homologues with the oestrogen receptor active site is discussed in terms of steroid stereochemistry.