The overall objective of the proposed research is to develop efficient and practical methodology for the asymmetric synthesis of alpha-amino acids based on carbon-carbon bond constructions of electrophilic glycine-derived templates. In addition, the free radical and electrocyclic couplings to these glycine-templates will be investigated. On the practical side, access to either D- or L- configured amino acids in high optical purity and chemical purity will be the primary utility of this research. These selective coupling reactions will be achieved by a careful study of the fundamental chemistry of hemi-amino acetals as substrates for cationic and radical reactions with a variety of organometallic reagents. A new organotin acetylide coupling reaction has been discovered and will be investigated as a means for preparing vinyl and alkynyl alpha-amino acids which have potent biological activities. Several second-generation chiral auxiliaries will be investigated to broaden the scope of the electrophilic glycine template concept. The new methodology will be demonstrated with total syntheses of several representative, complex amino acids.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040988-03
Application #
3298960
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1989-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
Schools of Arts and Sciences
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523