ORGN 507 |
| Yong Xu and Glenn D. Prestwich. Department of Medicinal Chemistry, University of Utah, 419 Wakara Way, STE 205, Salt Lake City, UT 84108 |
| Phosphatidylinositol polyphosphates (PtdInsPs) are key signaling molecules in cellular communication, and in particular phosphatidylinositol 3-phosphate (PtdIns(3)P) is crucial for vesicular trafficking of proteins. In order to dissect the complexities of this process, we designed novel metabolically-stabilized analogs of PtdIns(3)P as reporters of cell function. New asymmetric syntheses of metabolically stabilized (phosphatase-, kinase, and phospholipase-resistant) phosphatidylinositol 3-phosphate (PtdIns(3)P) analogs will be described. These analogs include methyl phosphonates, monofluoromethyl phosphonates, phosphorothioates, thiolophosphates and fluoromethylphosphonate functionalities. For several compounds, novel synthetic methodologies were developed to prepare these ligands. The resolution of the diastereomeric inositol ketal was used to get enantiomerically pure protected D-myo-inositol derivatives. Various phosphorylation reagents were employed to allow synthesis of PtdIns(3)P derivatives with different head groups. |
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Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic
9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster
Division of Organic Chemistry |