University of Illinois Urbana-Champaign

Synthesis of Functional Analogs of Non-Steroidal Estrogens

Kilbourn, Michael Robert

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Description

Title
Synthesis of Functional Analogs of Non-Steroidal Estrogens
Author(s)
Kilbourn, Michael Robert
Issue Date
1980
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Language
eng
Abstract
  • The synthesis and biochemical characteristics of several new, functionalized non-steroidal estrogens is reported. With the aim of developing an estrogen receptor-based radiopharmaceutical, two new iodinated estrogens, 1-(2'-iodo-4'-hydroxyphenyl)-2-(4'-hydroxyphenyl)butane and erythro-3-(2'-iodo-4'-hydroxyphenyl)-4-(4'-hydroxyphenyl)hexane (2'-iodohexestrol), were prepared. The relative binding affinities of these compounds for the estrogen receptor in vitro were 50 and 30, respectively, the highest yet achieved for estrogens bearing aryl iodides. For photoaffinity labeling studies of the estrogen receptor, a new photoreactive ligand, 1-(4'-hydroxyphenyl)-2-(2'-nitro-4'-methoxyphenyl)butane, was prepared by total synthesis (nine steps). This compound exhibited a low relative binding affinity for receptor, but a high (58%) inactivation efficiency (ability to destroy binding capacity) when photolyzed in the binding site.
  • The binding affinities of conformationally flexible ligands, such as the hexestrols and isobutestrol (1,2-bis(4'-hydroxyphenyl)butane), has been attributed to differing equilibrium populations of the antiperiplanar conformer; the conformer populations were determined by Force Field calculations of steric energy for rotations of model compounds. The data suggest that the receptor binds only the antiperiplanar, and not the synclinical, conformer of a flexible ligand.
Graduation Semester
1980
Type of Resource
text
Permalink
http://hdl.handle.net/2142/67222

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