SYNTHESIS OF 2-METHOXY AND 4-METHOXY EQUINE ESTROGENS

Article abstract of DOI:10.1016/0039-128X(87)90015-8

4-Methoxyequilin and 2-methoxyequilin were synthesized from the corresponding 4-bromoequilin and 2-iodoequilin derivatives, respectively, by nucleophilic displacement of halogen with methoxide ion in the presence of copper(II)chloride and 15-crown-5-ether. 4-Bromoequilin was prepared by reacting equilin with one equivalent of N-bromoacetamide. 2-Iodoequilin was prepared by reductive dehalogenation of 2,4-diiodoequilin, which in turn was obtained by treatment of equilin with two equivalents of iodine in methanolic ammonium hydroxide solution. 4-Methoxyequilenin and 2-methoxyequilenin were prepared from the corresponding 4-iodo- and 2-iodo-7ξ,8ξ-epoxyestrone derivatives, respectively.Nucleophilic displacement of iodine with methoxide ion was carried out as described earlier with simultaneous aromatization of the B ring leading to 4- and 2-methoxyequilenin derivatives.Alternatively, 4-methoxyequilenin was obtained from 4-methoxyequilin by selenium dioxide oxidation.