Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/34751
Title: Synthetic Studies of Azido-Inositols and Inositol-based Glycans
Authors: SANDIP PASARI
Keywords: Inositol lipids, azido-inositols, glycan synthesis
Issue Date: 29-Feb-2012
Source: SANDIP PASARI (2012-02-29). Synthetic Studies of Azido-Inositols and Inositol-based Glycans. ScholarBank@NUS Repository.
Abstract: The molecule inositol is extremely crucial to various cellular processes for both eukaryotes (e.g., yeast, mammalian cells) and prokaryotes. Inositol lipids (phosphatidyl inositol, phosphoinositides, etc) form components of cellular membranes and along with free inositols, participate in various signalling mechanisms. Higher inositol sphingolipids and glycophosphatidylinositol (GPI) anchors are known to be involved in host-pathogen interactions and in interactions of the cell within the extracellular environment. Here, we attempt to develop a tool to specifically target inositol lipids utilizing metabolic labelling using various synthetic inositol analogues modified with bioorthogonal groups (azide group). Thereafter, the synthesis of a new cyclooctyne fluorophore probe was explored for studying sub cellular location of the azido incorporated inositol lipids through copper free click chemistry. In addition, Plasmodium falciparum is the most lethal species for malaria disease causing majority of deaths. This parasite generates specific proteins that are transported to and are embedded in cell membrane of infected erythrocytes through GPI hosts. Since the biosynthesis of GPIs are essential for cell surface communications of these functional proteins to survive, inhibition of GPI bio-synthesis appear to be crucial for the development of various GPI-related drugs and vaccine candidates through the modification of the GPI glycan core. Here, we attempt to develop a short, convenient and practical synthesis of glycosylphosphatidyl inositol (GPI) of Plasmodium falcipuram through a (4+2) glycan coupling of phospholipidated pseudodisaccharide component and tetramannoside trichloroacetimidate. The suitably protected pseudodisaccharide component was achieved via a direct regioselective and stereoselective glycosylation of a myo-inositol orthoformate derivative with glucosaminyl donor. Furthermore, a liner convergent glycosylation approach towards the synthesis of tetramannoside glycan with terminally differentiated protecting group was studied to build up the glycan portion of malaria GPI.
URI: http://scholarbank.nus.edu.sg/handle/10635/34751
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