RUI: Metallanitrene-Mediated Amino Sugar Synthesis

Barnard College, New York NY

Investigators

Abstract

This project explores the use of intramolecular nitrene insertions for the preparation of amino sugars. Primary carbamates tethered within the sugar framework are the precursors of metal-complexed nitrenes for insertion into proximal carbon-carbon double bonds. Nucleophilic opening of the resulting aziridines provides a means for stereocontrolled glycosylation. This work focuses on how the stereochemical, conformational, and electronic properties of the glycal and pseudoglycal carbamate substrates influence the nitrene insertion event and the subsequent nucleophilic addition. A deeper understanding of these factors will permit application of the methodology to a wide variety of sugar carbamates and glycosyl acceptors. With the support of this award from the Chemical Synthesis Program, Professor Christian Rojas of the Department of Chemistry at Barnard College will explore synthetic methods for the preparation of amino sugars. Amino sugars play key roles in biological systems and in medicinal chemistry. For example, many cell-surface proteins are linked to amino sugar-containing fragments that serve as recognition elements for processes such as immune response. In addition, certain amino sugars act as potent inhibitors of enzyme action, others play important bio-structural roles, and some are therapeutically valuable antibiotics. Innovative synthetic methods for the preparation of amino sugars have the potential to open new avenues for the study of their biological properties and pharmacology. In addition, these synthetic studies will improve fundamental chemical understanding of routes to incorporate nitrogen atoms within complex organic molecules. Undergraduate students at Barnard, a liberal arts college for women, will be involved in all aspects of the project. They will contribute to the state of the art in organic chemical synthesis while receiving training that will enable them to pursue further study and careers in science, medicine, and technology.