139599-70-5Relevant academic research and scientific papers
The Structure and Function of Estrogens. XI. Synthesis of (+/-)-7(8->11α)abeo-Estradiol and its 9,11-Didehydro Derivative
Collins, David J.,Fallon, Gary D.,Skene, Colin E.
, p. 71 - 97 (2007/10/02)
Two approaches to the synthesis of (+/-)-7(8->11α)abeo-estra-1,3,5(10)triene-3,17β-diol (2a) from (+/-)-1β-t-butoxy-7aβ-methyl-2,3,3aα,6,7,7a-hexahydro-1H-inden-5(4H)-one (11) were studied.A pathway involving 6-alkylation of (11) with 2-(3'-methoxyphenyl)ethyl halides or sulfonate esters was unsuccessful, but conjugate addition of 3-methoxybenzyl nucleophiles with (+/-)-1β-t-butoxy-7aβ-methyl-6-methylene-2,3,3aα,6,7,7a-hexahydro-1H-inden-5(4H)-one (18), prepared from (11), led to (+/-)-1β-t-butoxy-6α--7aβ-methyl-2,3,3aα,6,7,7a-hexahydro-1H-inden-5(4H)-one (10a).Acid-catalyzed cyclization of (10a) afforded (+/-)-17β-t-butoxy-3-methoxy-7(8->11)abeo-estra-1,3,5(10),9(11)-tetraene (29) which upon lithium/ammonia reduction in the presence of diphenylmethane gave (+/-)-17β-t-butoxy-3-methoxy-7(8->11α)abeo-estra-1,3,5(10)-triene (31).Deprotection of (31) and (29) afforded (+/-)-7(8->11α)abeo-estra-1,3,5(10)-triene-3,17β-diol (2a) and (+/-)-7(8->11)abeo-estra-1,3,5(10),9(11)-tetraene-3,17β-diol (32), respectively. Alternatively, reaction of (+/-)-1β-t-butoxy-7aβ-methyl-6-methylene-2,3,3aα,6,7,7a-hexahydro-1H-inden-5(4H)-one (18) with 3-methoxybenzyl phenyl sulfoxide (23a) gave (1RS,3'SR,2RS,3a'SR,7a'SR)-3'-t-butoxy-2-(3''-methoxyphenyl)-3a'-methyl-2',3',3a',4',7',7a'-hexahydrospiroinden>-6'(1'H)-one (26), reductive cleavage of which with lithium/ammonia afforded (10a). The relative stereochemistries of (31) and of the spiro cyclopropyl ketone intermediate (26) were established unambiguously by X-ray crystallography.
