71505-81-2Relevant academic research and scientific papers
7α,11β-disubstituted estrogens: Probes for the shape of the ligand binding pocket in the estrogen receptor
Tedesco, Rosanna,Katzenellenbogen, John A.,Napolitano, Elio
, p. 2919 - 2924 (2007/10/03)
To investigate whether the estrogen receptor accommodates 7α and 11β substituents on estradiol in two subsites or in a single subsite, we have prepared three sets of ligands bearing single (7α or 11β) or double (7α and 11β) substituents and measured their binding affinity. The different behavior of each set precludes a definitive choice, but supports a two subsite model with some limitations.
5,6,11,12-Tetrahydrochrysenes: Synthesis of Rigid Stilbene Systems Designed To Be Fluorescent Ligands for the Estrogen Receptor
Hwang, Kwang-Jin,O'Neil, James P.,Katzenellenbogen, John A.
, p. 1262 - 1271 (2007/10/02)
We have prepared a series of tetrahydrochrysenes as fluorescent ligands for the estrogen receptor.The stilbene chromophore in this tetracyclic system is held rigid and is adorned with an electron-donating hydroxyl group at C-8 that corresponds to the phenolic hydroxyl of estrogens and an electron acceptor at C-2 to give a donor-acceptor fluorophore.Additional substituents at C-5 and C-11 provide additional bulk that improves receptor binding affinity without distorting the planar conjugated system.The tetrahydrochrysene core was prepared by an acyloin condensation of α-alkyl m-methoxyhydrocinnamate esters, followed by a double dehydrative cyclization.The cis and trans isomers of the alkyl substituted systems could be separated and their stereochemistry ascertained by X-ray crystallographic analysis; the trans isomer has the higher receptor binding affinity, and the derivative with ethyl substituents at C-5 and C-11 has the best affinity.The donor-acceptor systems were prepared by functional group manipulations on one of the aromatic methoxy groups: conversion to the trifluoromethanesulfonate was followed by a palladium-mediated carbonylation to give the acetyl derivative and methoxycarbonylation to give the ester.The ester was further elaborated to the amide and nitrile.The nitro compound was prepared by nitration of protio system, itself prepared by hydrogenolysis of the trifluoromethanesulfonate.As will be described later, these tetrahydrochrysenes provide a favorable combination of estrogen receptor binding affinity and long wavelength, high quantum yield fluorescence to make them useful as fluorescent ligands for the estrogen receptor.
The Structure and Function of Oestrogens. IX Synthesis of the trans Isomer of 5,5,10b-Trimethyl-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol
Collins, David J.,Cullen, John D.
, p. 735 - 744 (2007/10/02)
Alkylation of ketene methyl trimethylsilyl acetal (10) with 1ξ-acetoxy-6-methoxy-2-(p-methoxyphenyl)-2-methyl-1,2,3,4-tetrahydronaphthalene (9) in the presence of zinc iodide gave 84percent of methyl (1'RS,2'RS)-2-ethanoate (11a).Cyclization of the derived acid (11b) with methanesulfonic acid gave 89percent of 2,8-dimethoxy-10b-methyl-cis-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (12a), Clemmensen reduction of which afforded 52percent of 2,8-dimethoxy-4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene (12b).Oxidation of (12b) with dichlorodicyanobenzoquinone gave 70percent of the conjugated enone (4), which upon hydrogenation over 10percent palladium/charcoal gave a 5:1 ratio of 2,8-dimethoxy-10b-methyl-trans-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (14) and the cis isomer (12a).Exhaustive methylation of the trans ketone (14) yielded 49percent of 2,8-dimethoxy-5,5,10b-trimethyl-trans-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (16), which upon Clemmensen reduction followed by O-demethylation afforded 5,5,10b-trimethyl-trans-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol (2).
