The development of novel desymmetrization methods on a variety of phosphorus templates en route to structurally diverse alpha- aminophosphonic acids, phosphorus containing glycomimetics, and P-chiral synthons is the major goal of this study. These compounds have a wide array of applications and can serve as: i) potential inhibitors and probes of numerous enzymatic processes, ii) phosphorus analogs of sugars as potential glycosidase inhibitors, iii) conformationally restricted phosphorus analogs of amino acids, and iv) unique scaffolds for the construction of complex acyclic organic molecules. A novel desymmetrization strategy en route to highly functionalized phosphonates and phosphonamides possessing a stereogenic phosphorus atom (P-chiral) will serve as the cornerstone of the proposed method. This strategy involves: 1) the rapid assembly of pseudo C2-symmetrical phosphoryl templates; 2) the desymmetrization of these templates employing a variety of synthetic protocols; 3) the functionalization of the resulting building blocks en route to numerous acyclic alpha- aminophosphonic acids, phosphonoglycomimetics, and bicyclic P-chiral alpha-aminophosphonic acids as potential pharmacological agents; and 4) the stereocontrolled synthesis of an array of highly functionalized acyclic precursors to showcase the synthetic utility of these P-chiral building blocks. The proposed methods are unique in that a novel diastereotopic differentiation will be used to generate the P-chiral building blocks. The implementation of this method on phosphorus templates represents a new area in the utilization of molecular symmetry to generate chiral molecules. The primary focus of this study is the establishment of the """"""""phosphorus template method"""""""" as a new approach for the construction of complex organophosphorus containing molecules and as a new paradigm for acyclic stereocontrol.
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