New Chiral Phosphonates for Organocatalysis and Isolation and Chemical-Biology of Natural Products from Ontario Plants

Abstract

<p> The catalytic asymmetric transformation of carbonyl compounds via iminium and enamine intermediates using chiral amines as organocatalyst has grown remarkably over last decade. Various "metal-free" reactions including aldol, Mannich, Michael, alkylation and Knoevenagel types have now been reported efficiently using simple amino acids as the sole organocatalysts. Amongst these, proline has proven to be particularly useful as a general catalyst in such catalytic asymmetric syntheses due to its unique properties. Nonetheless, proline suffers inherent fundamental disadvantages as an organocatalyst in terms of its solubility in organic media, limiting reactions to polar aprotic solvents such as DMF or DMSO. We have been interested in the synthesis of derivatives of proline incorporating functional groups that would render the chiral secondary amine fully soluble in organic solvents such as THF or dichloromethane and others that could be employed in aqueous media. The synthesis of these catalysts and their application towards the asymmetric synthesis will be presented.</p> <p> The thesis also describes isolation and identification of natural products and synthesis of their semi-stabilised derivatives. Sakuranetin and dihydrowagonine were isolated from Prunus avium plant parts, menisadurilide was isolated from Dicentra spectabilis extracts while narciclasine was isolated from Narcissus pseudonarcissus plant parts. Semi-synthetic derivative, trans-dihydronarciclasine was prepared from natural product narciclasine. Both the derivatives were subjected to antifungal and human cytochrome inhibition activity and their correlation is explained. The Amaryllidaceae family alkaloids and their semi-synthetic derivatives were subjected to biological testing and an important structural property is correlated to their activities.</p>