# Development of Efficient Carbon Carbon Bond Formations for Novel Se-, S-, and O-Heterocycle Synthesis

> **NIH NIH R16** · WINSTON-SALEM STATE UNIVERSITY · 2024 · $61,218

## Abstract

NIH SuRE Project – Abstract
 Heterocycles account for more than 50% of all known organic compounds. Their rich
activities in biological systems are important for pharmaceuticals and natural products. Among
the top 200 brand name drugs, over 75% are heterocyclic compounds. In nature, heterocycles
are active components for defense, communication, and reproduction. Low regioselectivities,
low stereo-/enantioselectivities, lengthy synthetic sequences, and low overall yields in most
multi-step syntheses make it extremely challenging to provide sufficient quantities of desired
bioactive heterocycles for therapeutic purposes. This NIH SuRE proposal aims to develop and
utilize highly selective metal catalyzed carbon carbon bond formation reactions that will lead to
efficient synthesis of novel selenium, sulfur, and oxygen-containing heterocycles with rich
biological activities. This proposal also aims to develop multicomponent coupling processes for
rapid generation of functionality and complexity in heterocycles, a new selective merged
asymmetric conjugate addition-acylation as well as a merged conjugate addition-oxidation
strategy that will lead to the synthesis of new classes of bioactive selenium, sulfur-containing
heterocycles. The proposed new C-C bond formations and multicomponent reactions will
provide new opportunities for complex novel heterocycle synthesis including selenium-
heterocycles. The metal-catalyzed conjugate addition of nucleophiles onto polyenic Michael
acceptors is one of the most attractive and powerful C-C bond forming strategies for synthesis
of relevant molecules, as it provides opportunity for sequential generation of two or more
stereogenic centers in a straightforward fashion. The multicomponent reactions enabled by
direct trapping of metal enolates could provide powerful transformations for the formation of
multiple C-C bonds and chiral centers in a single pot. The resultant versatile heterocyclic
subunits and trapping of the metal enolates in situ will provide excellent opportunities for new
innovative approaches for novel complex heterocyle synthesis and drug discovery. Further
elaboration of this chemistry will likely allow the first enantioselective synthesis of very
important classes of heterocycles such as biselenoflavonoids, bithioflavonoids and bioactive
biflavonoids, potential small molecule therapeutics for Alzheimer’s disease. This SuRE project
is expected to significantly enhance and expand the research capacity towards a sustainable
research excellence at WSSU, a HBCU.

## Key facts

- **NIH application ID:** 11034361
- **Project number:** 3R16GM145541-03S1
- **Recipient organization:** WINSTON-SALEM STATE UNIVERSITY
- **Principal Investigator:** Fenghai Guo
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $61,218
- **Award type:** 3
- **Project period:** 2022-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11034361

## Citation

> US National Institutes of Health, RePORTER application 11034361, Development of Efficient Carbon Carbon Bond Formations for Novel Se-, S-, and O-Heterocycle Synthesis (3R16GM145541-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11034361. Licensed CC0.

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