Synthesis of Functional Analogs of Non-Steroidal Estrogens

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Kilbourn, Michael Robert

• Chemistry, Organic

Language dc:language

eng

Identifier

(UMI)AAI8017962

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/67222