Synthesis of Natural Products by Oxidative Dearomatization and Discovery of BRAT1 Degraders

NIH RePORTER · NIH · R15 · $441,469 · view on reporter.nih.gov ↗

Abstract

Proposal Summary Quaternary carbon centers are vital for the structural diversity of organic compounds, impacting the biological activity of natural products, pharmaceuticals, and materials. This proposal aims to develop oxidative conditions for the dearomatization of substituted phenols and achieve the total synthesis of Lycopodium alkaloids, with a focus on magellaninone and related alkaloids. The feasibility of manipulating product stereochemistry will be explored. Additionally, the total synthesis of curcusone A-D and the identification of potent BRAT1 degraders will be pursued. Synthetic protocols will be built upon, using readily available aromatic precursors. Molecular interactions between curcusone D and BRAT1 will guide the design of efficient protein degraders, with attachment point and linker modifications investigated. This research will advance the field of oxidative dearomatization and contribute to the development of novel therapeutic strategies.

Key facts

NIH application ID
10874296
Project number
1R15GM154274-01
Recipient
UNIVERSITY OF CENTRAL FLORIDA
Principal Investigator
Yu Yuan
Activity code
R15
Funding institute
NIH
Fiscal year
2024
Award amount
$441,469
Award type
1
Project period
2024-04-01 → 2027-03-31