The goal of the research outlined in this proposal is to investigate the scope of the palladium catalyzed dynamic kinetic asymmetric transformation (DYKAT) of racemic diene monoepoxides to enantiomerically pure 1,2-aminoalcohols and to apply this methodology to the synthesis of the natural products 2,5-dihydroxymethyl-3,4-dihydroxy- pyrrolidine, 1-deoxynojiromycin, swainsonine, 1-epi-alexine, and gualamycin, which are potent glycosidase inhibitors and represent four of the five general structural classes of these compounds. The reaction will be investigated by expanding the list of nitrogen nucleophiles and epoxides that can be used. In optimizing the reactions, advanced intermediates necessary for straightforward transformation into these inhibitors will be generated. Efficient enantioselective chemical syntheses by flexible routes using the proposed DYKAT methodology will provide a general synthetic strategy for the synthesis of a multitude of structurally similar alkaloids, which have been identified as potential pharmaceuticals in the therapeutic areas of cancer, diabetes, obesity, and anti-virals.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM069281-02
Application #
6984991
Study Section
Special Emphasis Panel (ZRG1-F04 (20))
Program Officer
Marino, Pamela
Project Start
2003-11-16
Project End
2005-11-15
Budget Start
2004-11-16
Budget End
2005-11-15
Support Year
2
Fiscal Year
2005
Total Cost
$43,976
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305