Synthesis of cis- and trans-3-fluoroacrylate, and inhibition of BCL6 targeting a non-reactive cysteine

Synthetic routes have been developed for two substrates for one project and an inhibitor in a second project. In the first project, synthetic routes were devised to make the cis- and trans-isomers of 3-flouroacrylate. In both cases, the compounds were successfully made in a four-step procedure. In future work, the compounds will be tested with cis- and trans-3-haloacrylate dehalogenase that has been shown to process the corresponding chloro- and bromo- isomers in an isomer-specific manner. These compounds might be processed like the other halo-acrylates (where the halo group if chloro or bromo) or might function as inhibitors if the enzyme proceeds through a halohydrin intermediate. In the second project, a potential inhibitor that targets the BTB-domain of BCL6 was made in a multi-step route. The compound builds on preliminary data that shows a “switchable electrophile” strategy can be used to selectively and irreversibly modify a cysteine within the corepressor peptide binding site in the BTB-domain of BCL6. Irreversible inhibition will block its function. These inhibitors are potential therapeutics for treating diffuse large B-cell lymphomas (DLBCLs) and triple negative breast cancers that are BCL6-dependent. In future work, the compound will be tested to validate the design principle. The results will guide the development of more potent and specific therapeutic agents.

Name thesis:degree_name

Master of Science in Pharmaceutical Sciences

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Medicinal Chemistry

Grantor

The University of Texas at Austin

Year dc:date.issued

2025

Author dc:creator

• Quintana Caban, Leugim J.

Advisor dc:contributor.advisor

• Whitman, Christian P.

Committee member dc:contributor.committeemember

• Hoffman, David W

• Dehalogenase
• Acrylate
• Suicide inhibitor
• BCL6

Identifier URI

https://doi.org/10.26153/tsw/63167

OAI identifier oai:identifier

oai:repositories.lib.utexas.edu:2152/135853