Synthesis of chiral polyoxygenated compounds via enzymatic and chemical methods.

摘要

Synthetic studies were performed to determine the utility of 4-hydroxy-2-ketoglutarate aldolase as a catalyst for organic synthesis. Chiral {dollar}alpha{dollar}-ketoacetals were explored for the diastereoselectivity of additions to the carbonyl functionality.; Chapter 1 describes the investigation of the utility of 4-hydroxy-2-ketoglutarate aldolase as a catalyst for organic synthesis. The aldolase was purified from wild type E. coli TG2 and the overexpressed mutant strain {dollar}rm DH5alpha Fspprime.{dollar} Substrate tolerance studies were conducted to reveal the utility of the E. coli enzyme. It was very selective towards its native substrates (pyruvate, glyoxylate, and oxalacetic acid). A preliminary attempt was made to take advantage of the decarboxylation activity to drive the reaction to the formation of the aldol adduct. Suggestions of future studies are discussed.; Chapter 2 describes studies of reactions of chiral acetals and their reactivities. A general synthesis of (4R*,5R*)-2-acyl-4,5-diphenyl-1,3-dioxolanes and the addition of alkylmagnesium bromides to these compounds. A survey of reaction conditions is carried out to obtain optimal diastereoselectivity. The addition reactions occur with high diastereoselectivity (typical selectivity ca. 90:10). An example addition reaction carried out on an optically active acetal proves the sense of asymmetric induction for addition of organomagnesium reagents to these {dollar}alpha{dollar}-ketoacetals. An explanation of the mechanism of asymmetric induction is given. Future use of this methodology is suggested via formation of chiral acetal oxime.