# Broadly Applicable, Small Molecule Catalysts for Stereoselective and Site-Selective Glycosylation Reactions

> **NIH NIH R01** · HARVARD UNIVERSITY · 2021 · $337,836

## Abstract

This project is directed toward the development of robust, practical, and general methods for glycosylating
nucleophiles with predictable stereoselectivity and regioselectivity. Despite extraordinary efforts and advances
over the past century, glycan synthesis remains a highly challenging endeavor largely reserved for specialists.
Given the unquestioned importance of carbohydrates in virtually all facets of biological chemistry, methods that
can be applied predictably and broadly for effecting glycosylations of molecules of interest are needed. Our
laboratory has helped pioneer the use of small-molecule chiral H-bond donors as catalysts for enantioselective
reactions. In an outgrowth of these studies, we have uncovered a new principle for effecting both
stereoselective and site-selective glycosylation reactions. Precisely tailored bisthiourea catalysts promote
stereospecific, invertive reactions of alcohol nucleophiles with glycosyl chlorides and glycosyl phosphates via
cooperative activation of both the nucleophile and the electrophile. Because the donors are quite stable and
exist predominantly and often exclusively in the α-configuration, and the catalysts are compatible with a wide
range of functionalities, this mode of catalysis represents a widely applicable approach to the creation of β-
glycosidic linkages. We will seek to develop the scope and limitations of the catalytic principle in the context of
model disaccharide couplings and the synthesis of glycosides of biologically important compounds. While
broadly general protocols are sought, we will focus our efforts on especially challenging cis-1,2-glycosidic
linkages in pyranosides and furanosides. We will also explore the ways by which the cooperative activation
mechanism can be applied to site-selective activation and glycosylation of unprotected sugars and other
polyfunctional nucelophiles. If developed fully and successfully, this methodology would greatly enable the
synthesis of biomedically relevant glycans, glycopeptides, glycoproteins, glycolipids, and microbial
polysaccharides and glycoconjugates by non-specialists.

## Key facts

- **NIH application ID:** 10106641
- **Project number:** 5R01GM132571-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** ERIC N JACOBSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,836
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106641

## Citation

> US National Institutes of Health, RePORTER application 10106641, Broadly Applicable, Small Molecule Catalysts for Stereoselective and Site-Selective Glycosylation Reactions (5R01GM132571-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10106641. Licensed CC0.

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