I. The design, synthesis and evaluation of L-ascorbic acid provitamins. II. Studies toward a rationally designed chiral lithium amide base for enantioselective deprotonation

Kenneth M Gigstad, Purdue University

Abstract

The preparation and evaluation of L-ascorbic acid pro-vitamins is described. Through a modification of the Reichstein-Grussner synthesis of ascorbic acid, three derivatives of L-xylo-2-hexulosonic acid, designed to release sc L-ascorbic acid in vivo, were synthesized. Differing molecules acylated by L-xylo-2-hexulosonic acid: glycolic acid, glycine and urea were used, giving rise to an ester, amide and imide, respectively. Of the three derivatives, the imide was shown to afford sc L-ascorbic acid most readily under conditions designed to mimic gastric juice, and the amide least readily. It is anticipated that these derivatives may find use in therapies in which slow release of sc L-ascorbic acid to the intestines or bloodstream is desired. The second area of research discussed is a study directed toward the design and synthesis of a chiral lithium amide base for the asymmetric formation of carbanions through non-bonded interactions. A chiral variant of the widely used lithium amide base LDA was prepared from methyl (S)-lactate. Through incorporation of a pendant heteroatom to provide an additional coordination site for lithium, a high level of enantiodiscrimination is expected through the formation of highly ordered transition state structures in the deprotonation of conformationally anchored cyclohexanones.

Degree

Ph.D.

Advisors

Lipton, Purdue University.

Subject Area

Organic chemistry

COinS