# Development of novel approaches for stereoselective construction of glycosidic linkages

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2020 · $593,344

## Abstract

Proposal abstract
 Complex oligosaccharides and glycoconjugates have been known to play critical roles innumerous biological
processes. However, extensive studies on glycobiology have been substantially hindered due to obstacles in
obtaining homogeneous carbohydrate structures. Over past years, chemical synthesis has demonstrated to be
a valuable and viable tool for preparation of significant quantities of homogenous structurally well-defined
carbohydrates, as heterogeneous glycoforms are usually isolated from natural sources. Despite remarkable
success has been achieved, the lack of mild, catalytic, easy-to-operate, and robust glycosylation methods for
stereoselective synthesis of complex α- and β-oligosaccharides still remains a challenge even for synthetic
carbohydrate chemists, let alone non-specialists.
 To address this challenge of critical importance in glycoscience, the proposal entails seven aims, which are
grouped into three themes. In Theme #1, a) gold catalysis are proposed to harness the soft acidic nature of
cationic Au(I) complexes in the development of mild and catalytic donor activation via either gold carbene
intermediates or a sulfide cyclization process, b) the robust and rather unique linear structure of Au(I) complexes
is to be exploited to develop an enzyme-mimicking synergistic acid and base catalysis en route to SN2
glycosylation, and c) a much more affordable and scalable silver catalysis is to be developed by Yu’s gold-based
versatile glycosylation chemistry. In Theme #2, stereoselective synthesis of β-mannoside type of glycosidic
linkages existing in microbial capsular oligosaccahrides and bacterial cell walls, such as 6-deoxy-β-D-manno-
heptopyranosides, 2-deoxy-2-amino-β-D-mannuronic acids, and β-D-mannosamines, will be achieved via a new
β-mannosylation we recently developed. In this approach, construction of these challenging glycosidic linkages
will be achieved via cesium carbonate-mediated anomeric SN2 O-alkylation of corresponding lactol donors with
sugar triflates. With those glycosylation methods developed, Theme # 3 will feature them in an expedient
synthesis of a hexasaccharide repeat units from Bacillus anthracis cell walls.
 These aims will be implemented via team effort and by harnessing the expertise of both the Zhu group and
the Zhang lab. The new methods developed will be first validated internally and then in the fourth year cross-
validated by Prof. Xuefei Huang’s lab at MSU.
 Ultimately, the glycosylation strategies developed in this proposal would be adopted by non-specialists for
the synthesis of oligosaccharides or carbohydrate libraries for biological studies or medical purpose.

## Key facts

- **NIH application ID:** 9935971
- **Project number:** 5U01GM125289-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Liming Zhang
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $593,344
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935971

## Citation

> US National Institutes of Health, RePORTER application 9935971, Development of novel approaches for stereoselective construction of glycosidic linkages (5U01GM125289-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935971. Licensed CC0.

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