Mechanistic investigation of the Staudinger ligation

ORGN 677

Fiona L. Lin, fionalin@berkeley.edu1, Helen M. Hoyt, hhoyt@uclink.berkeley.edu1, Herman van Halbeek, hvanhalbeek@purcell.cchem.berkeley.edu1, Robert G Bergman1, and Carolyn R. Bertozzi, bertozzi@cchem.berkeley.edu2. (1) Department of Chemistry, University of California, Berkeley, CA 94720, (2) Department of Chemistry and Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720
The Staudinger ligation is a powerful chemoselective ligation reaction that has found widespread usage in the field of chemical biology including in vitro and in vivo labeling of cell surface glycoconjugates and proteins, proteomics studies and synthesis of N-linked glycopeptides. Despite its general use, a systematic and detailed mechanistic study of the Staudinger ligation has not been described. Here we report our efforts towards the understanding of the mechanism of this transformation via kinetics and Hammett analyses, investigation of solvent effects and the isolation of a reaction intermediate. Results obtained in this study provide insights for optimization of parameters to improve reaction yields and rates, and serve as a platform for improved design of phosphine reagents.
 

Physical Organic Chemistry: Calculations, Mechanisms, Photochemistry, and High-Energy Species
1:00 PM-5:00 PM, Wednesday, 16 March 2005 Convention Center -- Room 11A, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005