Synthesis of Novel Types of Polyester Glycodendrimers and the Development and Applications of an Efficient Alternative to Multistep Regioselective Esterification in Diols and Polyols

Abstract

Polyester dendrimers are attractive for biological applications because they are biodegradable and non-toxic. The preparation of a variety of core molecules that are compatible with deprotection using hydrogenolysis is presented. Previous syntheses of polyester dendrimers have mainly focused on the use of dibranched building blocks or dendrons. Chemistry was developed for the synthesis of novel tribranched dendrons and lower generation dendrimers have been prepared. It was found that formation of successive generations using tribranched dendrons was not possible, presumably because of steric hindrance, but dendrimers containing alternating generations of dibranched and tribranched dendrons could be formed. In the search for a mild esterification method which would allow convergent synthesis of dendrimers, it was demonstrated that coupling agents namely, TBTU, TATU, and COMU are efficient promoters of ester bond formation between carboxylic acids and all types of alcohols in the presence of organic bases. It was shown that regioselective esterification of diols and polyols is possible based on whether the alcohols are primary, secondary, or tertiary, with choice of base and coupling agent. The base sensitivity of the TBTU-promoted esterification was used in the preparation of a library of the Lyme disease antigens termed Borrelia burgdorferi glycolipid 1 that contain esters of different fatty acids connected to O-6 of cholesteryl ?-D-galactopyranoside. In addition, the direct synthesis of maradolipids from the dauer form of the nematode Caenorhabditis elegans, and other trehalose 6-monoesters and 6,6’-diesters was demonstrated. Finally, novel types of polyester glycodendrimers have been synthesized using click chemistry to attach ?-D-mannopyranosyl glycosides bearing alkyne groups at the termini of their aglycones to polyester dendrimers with terminal azide groups, and these will be evaluated as anti adhesion drugs against urinary tract infections.