Synthetic Investigations in Chemical Probe Development Part 1: Design and Synthesis of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis of 2,8-Dihydroxychrysene

Author

Rachel Irene Hammond, University of MississippiFollow

Date of Award

Spring 5-8-2022

Document Type

Undergraduate Thesis

Department

Chemistry and Biochemistry

First Advisor

John Rimoldi

Second Advisor

Rama Gadepalli

Third Advisor

Daniell Mattern

Relational Format

Dissertation/Thesis

Abstract

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired 2,8-dimethoxychrysene was assembled in five steps from 3-(3-methoxyphenyl)propanoic acid, which upon esterification was linked via acyloin condensation to afford a bis(silyloxy)alkene that underwent cyclization and dehydrogenation via polyphosphoric acid and sulfur fusion, respectively. Demethylation using boron tribromide afforded the diol, provided that workup conditions were optimized to prevent byproduct addition over the olefinic 5,6 bond. The synthesized 2,8-dihydroxychrysene will next undergo toxicological analysis of metabolized products. Although the investigations reported here are vastly dissimilar, their dissimilarities have allowed for a diverse exploration in synthetic organic chemistry techniques that have been altogether effective in preparation for future synthetic pursuits.

Recommended Citation

Hammond, Rachel Irene, "Synthetic Investigations in Chemical Probe Development Part 1: Design and Synthesis of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis of 2,8-Dihydroxychrysene" (2022). Honors Theses. 2671.
https://egrove.olemiss.edu/hon_thesis/2671

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