Date of Award

5-2025

Degree Type

Honors College Thesis

Academic Program

Chemistry BS

Department

Chemistry and Biochemistry

First Advisor

Douglas Masterson, Ph.D

Advisor Department

Chemistry and Biochemistry

Abstract

The 5-hydroxytryptamine1A (5-HT1A) receptor is a key target in the treatment of various neuropsychiatric conditions, and the development of selective antagonists offers promising therapeutic potential.24 This study aimed to develop a synthetic analog of LY426965, a selective 5-HT1A receptor antagonist. The synthetic route was initiated from dimethyl-2-phenylmalonate, employing pig liver esterase (PLE) as an enantioselective biocatalyst to achieve regioselective hydrolysis of one ester moiety in the malonic diester intermediate.17 Through a series of stereochemically controlled transformations, a new intermediate was successfully synthesized. Although the target molecule was not obtained, a new compound was synthesized that allows for further research. The proposed structural analog involves the substitution of the phenyl ring with a cyclohexyl group. This work contributes to the foundation for the efficient and scalable synthesis of novel 5-HT1A antagonists and to the broader efforts of developing cost-effective central nervous system-active therapeutics.

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