Title

Part I. The synthesis of 5-hydroxymethyl-3-nucleobase-2-pyrrolidinones as potential anti-HIV compounds. Part II. Conducting polymers as chemical reagents: The use of poly-(3,4-ethylenedioxy thiophene) in the Friedel-Crafts alkylation of aromatic rings with alcohols

Date of Completion

January 2005

Keywords

Chemistry, Organic|Chemistry, Pharmaceutical|Chemistry, Polymer

Degree

Ph.D.

Abstract

Part I. A number of 5-hydroxymethyl-3-nucleobase cyclic molecules exist, and are known to possess a range of anti-HIV activity. This class of compounds is also known to possess a wide range of antibiotic activity and anticancer activity. One of the few carbocycles not explored is the lactam ring. To fill this void, we targeted 5-hydroxymethyl-3-nucleobase-2-pyrrolidinones as potential anti-HIV compounds. The first generation synthesis had to be abandoned due to an unforeseen stereochemical issue. The modifications made to the synthetic protocol allowed for the synthesis of two targets: 3-N 9-guaninyl-5-hydroxymethyl-2-pyrrolidinone (1a (as a crude mixture)) and 3-N9-adeninyl-5-hydroxymethyl-2-pyrrolidinone ( 1b). ^ Starting from the commercially available trans-4-hydroxy-L-proline, the immediate precursor to 1a was prepared in 9 steps, and 7.5 % overall yield. Target 1b was also prepared from the same starting material in 10 steps, and an overall yield of 3.4%. The biological testing of 1a is pending, but 1b was found to be inactive as an anti-HIV agent, and as an antibiotic. ^ Part II. Polymers in general, and conducting polymers specifically, are not considered to be chemical reagents. We have found that the conducting polymer poly-(3,4-ethylenedioxy-thiophene) facilitates chemical reactions with alcohols. The observed reactivity includes oxidation to the corresponding aldehyde or ketone, and acid-like chemistry where substitution reactions or a Friedel-Crafts alkylation of an aromatic ring by the alcohol was observed. The scope of the Friedel-Crafts reactivity was explored and it was found that the reactivity is similar to that of other catalysts for the Friedel-Crafts alkylation of alcohols. The benzylic alcohols tended to be the most efficient, followed by the allylic and finally, the aliphatic alcohols, which tended to show little to no effectiveness at the alkylation of aromatic rings. ^