Studies of chirality, supramolecular structure, order and reactivity in and from biological systems.

摘要

Glycosyl diacylglycerols are excellent lipids for the formation of both bi and monolayer lamellar systems but they are generally not commercially available or chemically easily accessible. Several glycolipids designed to be easily accessible structural surrogates of monoglucosyl diacylglycerol (MGDG) have been synthesized. The general strategy of replacing the natural glycerol linker with a chiral 1,2,4-butanetriol simplified the synthesis significantly. A novel acetal linkage was introduced in one of the design, which brings chemically and physically tunable new properties in a glycolipid. These include base stability, resistance to the degradation by phospholipase and other esterase activities present in all cellular systems, increased mobility of the headgroup, possibilities of new packing arrangements and the potential for use in encapsulation strategies using liposomes where a decrease in pH is used as the environmental cue for release. Another two MGDG analogs were close structural precursors of potent anti-HIV agent sulfoquinovosyl diacylglycerol (SQDG). The quick access to a close SQDG analog from these MGDG analogs was attempted.; It is known that biomembranes play a crucial role in living cells by serving both as selective barriers for transport and as sites for molecular recognition and catalysis. I am interested in whether and how the packing order, symmetry properties, steric and proximity factors of membrane systems or other highly ordered supramolecular ensembles encode the regio- and stereo-regularities of reactions occurring on their surfaces. A series of glycolipids were designed, synthesized, and the predominant supramolecular structures they form were characterized. By initiating transglycosylation reactions among these systems and analyzing the regio- and stereo-regularity of the transglycosylation products, I tried to shed some light on the encodement of 1-D linkage and sequence information in the 2-D organization of supramolecular ensembles.; Chiral beta-hydroxy acids and gamma-hydroxy acids are important pharmaceutical intermediates. General routes towards alkenyl-containing 5 and 6-carbon chiral beta-hydroxy acids and gamma-hydroxy acids using carbohydrates as chiral synthon were developed. These intermediates are also logical precursors of corresponding amino acids. An increasingly important pharmaceutical target Vigabatrin RTM (gamma-vinyl-gamma-amino-butyric acid) was synthesized in a short synthetic route from its chiral gamma-hydroxy acid precursor using the developed strategy.