# Selective Nitrogen Atom Transfer for Applications in Biomedical Sciences

> **NIH NIH R35** · BRANDEIS UNIVERSITY · 2021 · $406,250

## Abstract

Project Summary/Abstract
 The long-term goal of our research program is to develop general and selective nitrogen atom transfer
methods that can generate new molecular entities through precise functionalization of both complex molecules
and simple commodity chemicals. A large number of therapeutic molecules and small-molecule biological
probes have at least one nitrogen atom; therefore, synthetic methods based on direct nitrogen atom transfer to
organic molecules are important synthetic tools. Although a variety of valuable olefin amination methods have
been established, new selective nitrogen atom transfer methods based on novel reaction mechanisms are still
urgently needed which can be effective and exquisitely selective across a broad range of substrates and
thereby fill important gaps of existing synthetic approaches. Inspired by these outstanding synthetic challenges,
we intend to discover new reactivity in three directions of selective nitrogen atom transfer and we will develop
new synthetic methods that hold the promise to become unique and enabling tools for organic synthesis and
medicinal chemistry.
 First, we will explore uncharted territory in iron catalysis and discover the iron-catalyzed olefin
amination that does not involve radical intermediates and would thereby be compatible with a range of
functional groups which are problematic with the alternative amination methods. Completion of this project will
provide effective methods for selective olefin amination in complex molecules. Next, we will discover a
fundamentally new cis-glycosylation reaction that does not proceed through an oxocarbenium ion and develop
a series of iron-catalyzed one-step glycal amidoglycosylation methods that efficiently connect glycals and
glycosyl acceptors to selectively afford 1,2-cis-amido glycosidic linkages that are known to be difficult to form
reliably in high stereoselectivity using traditional glycosylation methods. Completion of this project will provide
an array of unique methods that fill an important gap in complex-carbohydrate synthesis. Furthermore, we will
explore an entirely new HN3 activation mechanism and develop a range of metal-free methods that enable
direct addition of HN3 at ambient temperature across a wide variety of unactivated olefins for azido-group
labeling of complex molecules. Completion of this project will provide a valuable tool of azido-group labeling for
applications in synthetic chemistry and chemical biology.

## Key facts

- **NIH application ID:** 10200095
- **Project number:** 5R35GM134926-02
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Hao Xu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $406,250
- **Award type:** 5
- **Project period:** 2020-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200095

## Citation

> US National Institutes of Health, RePORTER application 10200095, Selective Nitrogen Atom Transfer for Applications in Biomedical Sciences (5R35GM134926-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200095. Licensed CC0.

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