(I) Development of an Inexpensive Carbohydrate Derivative Used as a Chiral Auxiliary in the Synthesis of alpha-Hydroxy Carboxylic Acids. (II) Synthesis of a Potential Carrier for Copper Ions Designed to Be Transported by P-Glycoprotein.

Abstract

1. Development of an Inexpensive Carbohydrate Derivative Used as a Chiral Auxiliary in the Synthesis of alpha-Hydroxy Carboxylic Acids

Protected alpha-hydroxy carboxylic acids were synthesized in moderate yield and high diastereoselectivity by alkylation of glycolate (alpha-hydroxy acetate) enolates using a D-fructose-derived chiral auxiliary. The new chiral center was assigned the R configuration based on comparisons of optical rotations and on one crystal structure analysis. This alkylation methodology is compatible with several hydroxyl protecting groups. The free hydroxy acids were obtained upon removal of the protecting group from the hydroxyl functionality followed by saponification.

2. Synthesis of a Potential Carrier for Copper Ions Designed to Be Transported by P-Glycoprotein

Poisoning by heavy metals has traditionally been treated with a handful of nonspecific, highly polar chelating agents. Although the present set of chelators has proven to be valuable as therapeutics, their lack of specificity sometimes results in leaching of essential minerals and their high polarity limits their excretion, such that the metal-chelate complexes are primarily removed by the kidneys.

We have developed a potential transporter for copper ions, consisting of a chelator conjugated to a P-glycoprotein transporter substrate. We hypothesize that upon complexation to copper, the complex can be removed by the P-glycoprotein active transporter. Assays that will determine the metal-binding and biological transport properties of the conjugates are planned for later.