ORGN 602

Directed asymmetric assembly of simple achiral building blocks into stereochemically complex molecules like carbohydrates and polyketides has long been the purview of nature’s enzymes. Our approach to this problem began in 1997 when we embarked upon studies exploring the similarity between proline and aldolase antibody-catalyzed reactions. Recently, these studies have allowed us to describe the first direct organocatalytic asymmetric aldehyde additions in Michael, aldol, and Mannich-type reaction manifolds. Aldehyde addition reactions are of particular significance to assembly strategies since the aldehyde functionality found in the products of these reactions provides versatile chemical handle for further diversification. We have now applied this strategy in aldol, Mannich, Micheal, and Diels-Alder reaction manifolds to provide for the direct assembly or one-pot syntheses of sugars, polyketides, unusual amino acids, amino alcohols and functionalized ketones.