# Methods for Chemo- and Site-Selective C-O activation in Bioactive Natural Products

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $303,657

## Abstract

Abstract
Late stage functionalization (LSF) is a synthetic strategy to derivatize medicinally interesting
compounds to optimize key properties such as bioactivity, pharmacokinetics, etc. The challenge
to the synthetic methodology for doing so is one of chemo- and site-selectivity as most such
species are multi-functional, and even display multiple copies of a target functional group. We
outline an approach that utilizes oxophilic silylium and borenium ions to target for subsequent
derivatization, the C–O bonds common in bioactive natural products (NPs), all under catalyst or
reagent control. The methods to be investigated first heterolytically cleave Si–X and B–X bonds
(X= H, allyl, N3, etc), and then sequences their reactivity to achieve the C–O
activation/functionalization goal. Fluoroaryl borane Lewis acids such as B(C6F5)3, BCF, are
effective catalysts for generating the key reactive ion pairs and they will be optimized via high
throughput screening techniques.

## Key facts

- **NIH application ID:** 10246926
- **Project number:** 5R01GM130693-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** MICHEL R GAGNE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $303,657
- **Award type:** 5
- **Project period:** 2018-09-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246926

## Citation

> US National Institutes of Health, RePORTER application 10246926, Methods for Chemo- and Site-Selective C-O activation in Bioactive Natural Products (5R01GM130693-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246926. Licensed CC0.

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