The proposed research program would develop methods, based on alkoxycarbinyl radicals, for the asymmetric synthesis of highly oxygenated cyclic and acyclic systems. These methods would be applied to the synthesis of natural products, designed biological probes, and enzyme inhibitors, and thus would be of benefit in the medicinal chemistry arena in general. Specific research areas to be addressed include: 1. Development of new methods to synthesize highly oxygenated bridged ring systems using alkoxycarbinyl radicals. These methods would be applied to the total synthesis of zaragozic acid (squalestatin). Ready access to the zaragozic acid ring system would allow the design and synthesis of novel inhibitors of enzymes that utilize diphosphate- containing substrates. 2. Development of new methods for the synthesis of complex spirocyclic ring systems, including spiroethers and spiroketals, based on alkoxycarbinyl radicals. These methods would be applied to the synthesis of conformationally constrained glycopeptides which, in turn, would be useful for probing glycoprotein structure and function in biological systems. These compounds would be particularly useful for investigations into biological processes involving carbohydrate recognition.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053496-04
Application #
6342914
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
1998-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
4
Fiscal Year
2001
Total Cost
$148,227
Indirect Cost
Name
University of Colorado at Boulder
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309