Synthesis of 2-methoxy and 4-methoxy equine estrogens.
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-Methoxy-equilenin and 2-methoxyequilenin were prepared from the corresponding 4-iodo- and 2-iodo-7 epsilon, 8 epsilon-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.
Rao
P N
PN
Department of Organic Chemistry, Southwest Foundation for Biomedical Research, San Antonio, TX 78284.
Somawardhana
C W
CW
D000818:Animals; D004855:Equilenin / Q000031:analogs & derivatives / Q000138:chemical synthesis; D004857:Equilin / Q000031:analogs & derivatives / Q000138:chemical synthesis; D004967:Estrogens / Q000138:chemical synthesis*; D006736:Horses
C056917:4-methoxyequilin; D004967:Estrogens; D004857:Equilin; C056916:2-methoxyequilin; C056919:4-methoxyequilenin; C056918:2-methoxyequilenin; D004855:Equilenin