The overarching goal of this proposal is the development of new methods to generate enantioenriched organic compounds. These products are valuable precursors to more elaborate small molecules that are medicinal agents and/or more complex biologically active natural products. The proposed methods specifically target the concise synthesis of 1-amino acids, 1,2-diamino acids, 1-aminophosphonic acids and chiral secondary amines. These methods are based on the development of chiral proton catalysts as new chiral, non-racemic reagents for enantioselective synthesis. The complexes are readily prepared organocatalysts, and are often bench stable solids. They are metal free, and therefore may be referred to as organic catalysts. These studies have the potential to impact the synthesis of both small molecule and """"""""biologic"""""""" therapeutic agents. Moreover, the methods enable the metal-free production of functionally dense, single enantiomer (and diastereomer) organic compounds.

Public Health Relevance

This proposal describes the development of chiral small molecule organocatalysts and the corresponding enantioselective reactions. In a single step, chiral nonracemic secondary amines and their derivatives (1-amino acids, 1-aminophosphonates, 1,2- diamino acids) are produced in stereochemically enriched form. These chemical commodities are common subunits of biologically active natural products, biologics, and small molecule therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM084333-03
Application #
8110644
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2009-05-01
Project End
2013-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
3
Fiscal Year
2011
Total Cost
$254,459
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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