Abstract: Phosphorus containing compounds have gained considerable attention due to their diverse biological and chemical profiles. A number of P-heterocycles have shown potent biological activity, and have become attractive targets as rationally designed small molecules. We are interested in continuing to build a library of highly functionalized heterocyclic phosphorus-containing compounds of varied chemical and biological interests. In out pursuit of novel P-heterocycles, we have recently become interested in the synthesis of amino acid-based phosphorus containing compounds that may have potentials as HIV-1 protease-inhibitors. Our efforts have largely been driven by the development of a number of cyclic urea-based HIV-1 protease inhibitors at Dupont-Merck that gave promising biological activity.