SYNTHETIC STUDIES OF PHOSPHONATE DERIVATIVES
Gregorio Valentin Sanchez, Jr.
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
Copyright 2006 Gregorio Valentin Sanchez, Jr.
Pyrophosphonate analogs such as methylenebisphosphonates and phosphonoacetates have applications in pharmaceutical chemistry and also in material sciences. Herein, a series of synthetic studies focusing on the preparation of potentially useful new organophosphorus compounds are presented. In Chapter 1, the addition of organometallic reagents to carbonylbisphosphonate and oxophosphonoacetate alkyl esters to generate a-hydroxy, a-substituted methylenebisphosphonate or phosphonoacetate alkyl esters is investigated. Chapter 2 discusses synthetic approaches to branched (E)-(hydroxyimino)(dihydroxyphosphinyl)acetic acid ligands and their possible application as metal chelating agents. Finally, Chapter 3 presents the hypochlorite oxidation of diazomethylenebisphosphonate alkyl esters with various alcohols for use in synthesis of nucleoside 5'-triphosphate carbonylbisphosphonate analogs.