Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Chemistry

First Advisor's Name

Kathleen S. Rein

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Stanislaw Wnuk

Third Advisor's Name

Philip Stoddard

Fourth Advisor's Name

Fenfei Leng

Fifth Advisor's Name

John T. Landrum

Date of Defense

7-17-2006

Abstract

The kainoids are a class of non-proteinogenic pyrrolidine dicarboxylates that exhibit both excitatory and excitotoxic activities. These activities are a result of the ability of the kainoids to act as glutamate receptor agonists by activating ionotropic glutamate receptors. The parent of this group of compounds is x-kainic acid. Kainic acid is isolated from the seaweed Diginea simplex and has been used in Asian countries as a treatment for intestinal worms in children. In addition it is used extensively by neuropharmacologists for the study of glutamate receptors. Several years ago, the world's sole supplier of kainic acid discontinued this product. Since that time, other sources have appeared, however, the price of kainic acid remains significantly higher than it once was. We have thus been working on synthesizing aza analogs of kainoids which would be less costly but potentially potent alternatives to kainic acid via the dipolar cycloadditions of diazoalkanes with trans diethyl glutaconate. These 1, 3-dipolar cycloadditions yielded 2- pyrazolines or pyrazoles. The 2-pyrazolines may be precursors to aza analogs of kainoids. The regioselectivity of these 1, 3-dipolar cycloadditions and isomerization of the 1- pyrazolines to 2-pyrazolines was evaluated. Reductions of the 2-pyrazolines yielded aza analogs of kainoids.

Identifier

FI14062265

Comments

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