Metal-mediated synthesis of stable glycopeptide mimics

ORGN 317

Brian HM. Kuijpers, B.Kuijpers@science.ru.nl1, Stan Groothuys, s.groothuys@science.ru.nl1, A. R. Keereweer1, Guido CT. Dijkmans1, Richard H. Blaauw, richard.blaauw@chiralix.com2, Peter JLM. Quaedflieg3, Floris L. van Delft1, and Floris P. J. T. Rutjes1. (1) Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, Nijmegen, 6525 ED, Netherlands, (2) Chiralix B.V, Toernooiveld 100, 6525 EC Nijmegen, Netherlands, (3) DSM Research, PO Box 18, Geleen, 6160 MD, Netherlands
Glycopeptides play a crucial role in a number of biochemical pathways. Investigation of their biological role is generally hampered by the sensitivity of the glycosidic (acetal) bond. We wish to report the synthesis of four different chemically and metabolically stable isostere classes, using either a metathesis/cyclization strategy or a Cu(I)-catalyzed [3+2] cycloaddition. The latter methodology allowed us to develop high yielding syntheses of both N- and C-linked triazologlycopeptides of variable length. Further modification of this methodology allowed us to synthesize trisubstituted 4-bromo-[1,2,3]-triazoles from organic azides and bromo-acetylenes in a single step. Finally, the results of incorporation of such isosteres in biologically active glycopeptides will be detailed.

 

Metal-Mediated Reactions and Syntheses
1:00 PM-5:00 PM, Monday, 11 September 2006 Moscone Center -- Room 133, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006