Date of Award

1-1-2010

Document Type

Campus Access Dissertation

Department

Chemistry and Biochemistry

Sub-Department

Chemistry

First Advisor

Sheryl L. Wiskur

Abstract

Part 1

Homoallylic alcohols are versatile synthons in natural product synthesis. They are most efficiently generated by allylation of aldehydes. Classically metal-based Lewis acids are frequently used to catalyze this process. These Lewis acids are inherently sensitive to air and moisture and thus require strictly anhydrous reaction conditions. Recent developments in the field of catalysis have found chiral organic Lewis bases to be efficient in catalyzing the asymmetric allylation of aldehydes, among them are formamide catalysts. In this study, structure and activity relationship evaluations were carried out using commercially available amides and formamides to investigate their effectiveness on activating the allylation of aldehydes. Results from this study led to the design of new chiral formamide catalysts with mono-, bis- and tri- formyl functional group. It was found that diformyls 5, 6, 7 and 8 were effective in the activation of the allylation with both aromatic and aliphatic aldehydes by allyltrichlorosilane giving up to 84% yield. Asymmetric allylation catalyzed by these formamides are modestly achieved at up to 14% ee. Additional fine tuning of catalyst structure is expected to improve asymmetric induction of the allylation of aldehydes.

Part 2

Domoic acid (DA), produced by marine diatom species in the genus Pseudo-nitzschia, is a potent excitotoxin known to cause amnesic shellfish poisoning, brain damage, and death in severe cases. Structurally, domoic acid is an analog of the amino acid glutamic acid and the excitatory neurotoxin kainic acid. The availability of these potent neurotoxins is critical for the studying of their pharmacology and treatment of neuro diseases in human. Both domoic and kainic acid belong to the family of kainoids which possess a common pyrrolidine ring with three contiguous stereocenters. There have been multiple total syntheses of kainic acid, but only one synthesis of domoic acid reported. The structure of kainic acid and domoic acid diverts at the C-4 side chain of the pyrrolidine ring. This point of differentiation inspires a parallel synthesis where insertion of a precursor of the domoic acid C-4 side chain into the pyrrolidine frame work of kainic acid intermediate, via alkene cross metathesis, would lead to domoic acid. Studies towards the synthesis of the vinyl side chain of domoic acid were carried out using commercially available chiral synthon (R)-2-chloropropionic acid methyl ester.

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