CONJUGATES OF STEROIDS AND ANTI-CANCER AGENTS. III. THE SYNTHESIS OF ESTRYNAMINE AND CERTAIN DERIVATIVES

Article abstract of DOI:10.1016/0039-128X(86)90005-X

Propargyl amine was protected by condensing it with 2,5-hexanedione to give 2,5-dimethyl-N-(2'-propyn-1'-yl)pyrrole (2).The latter was converted to the corresponding Grignard reagent with ethylmagnesium bromide, and then condensed with estrone tetrahydropyranyl ether to give 17α-<3'-(2'',5''-dimethyl-1''-pyrryl)-1'-propyn-1'-yl>-1,3,5(10)-estratriene-3,17β-diol 3-tetrahydropyranyl ether (3), in 85percent yield.Acetic acid and methanol cleaved the tetrahydropyranyl ether group, and hydroxylamine and sodium bicarbonate cleaved the pyrrole ring to give 17α-(3'-amino-1'-propyn-1'-yl)-1,3,5(10)-estratriene-3,17β-diol (1), estrynamine.Several derivatives and analogs of 1 were also synthesized.Estrynamine binds to estrogen receptor with an RBA of 0.0045 (estradiol = 1.0).Several of the compounds, including estrynamine, are weak estrogens (stimulation of prolactin synthesis).