# Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $447,006

## Abstract

Project Summary / Abstract
Rapid and reliable access to synthetically-derived chemical structures plays an essential role in many aspects
of biomedical research. The underlying objective of this proposal is to provide fundamentally new strategies for
highly selective bond formations that will enable more rapid and efficient access to biologically active
compounds of potential therapeutic value. A suite of new reactions will be developed that rely on the boron-
catalyzed coupling of organofluorine and organosilane substrates. Glycosylation reactions that rely on this
reactivity paradigm will be developed in concert with catalyst design, mechanistic study, and computational
evaluation. Robust methods that enable efficient assembly of glycosidic bonds with high degrees of
stereocontrol and broad functional group tolerance will allow access to any desired stereochemical outcome
while allowing a platform for iterative assembly of complex oligosaccharides. New late transition metal-
catalyzed processes will be developed utilizing the framework of connecting organofluorine with organosilane
substrates using boron co-catalysis. Methods where remote complexation of fluorine allows leaving groups to
be activated on demand will developed as a general strategy for applications in carbohydrate chemistry and in
carbon-carbon bond-forming methodology. Following the above focus on the development of new catalytic
methods, approaches to the efficient assembly of glycosylated structures will be pursued to provide new
methods for accessing novel chemical probes and potential therapeutic agents. This component will include
developing new strategies for accessing rare carbohydrates and for the stereoselective glycodiversification of
peptides, natural products, and complex synthetic intermediates. Methods for tailoring complex naturally
occurring and synthetic structures will include derivatization of existing hydroxyl functionality or biocatalytic
functionalization of unactivated C-H bonds. These capabilities will serve as a foundation for a broad array of
collaborative studies including the discovery of new antimicrobial and anticancer therapeutic agents and new
chemical probes to provide insight into diverse biological questions such as mechanisms of transcriptional
activation and enzymatic degradation of host and dietary oligosaccharides. The synthetic approaches
developed represent a merger of rarely combined fields of chemistry and biology: main group element
catalysis, transition metal catalysis, carbohydrate chemistry, and biocatalysis. The unique multidisciplinary
perspective allows examination of strategies that cannot be addressed by conventional approaches. The
improved entries to biomedically important structures made possible by this research will enable their biological
function and therapeutic potential to be more efficiently studied.

## Key facts

- **NIH application ID:** 10378698
- **Project number:** 5R35GM118133-07
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JOHN MONTGOMERY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $447,006
- **Award type:** 5
- **Project period:** 2016-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378698

## Citation

> US National Institutes of Health, RePORTER application 10378698, Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis (5R35GM118133-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10378698. Licensed CC0.

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