Ifosfamide analog, folate-tethered chemotherapeutic agents: Synthesis and biological evaluation
Abstract
Ifosphamide analogs are synthesized which are designed to activate at physiologic pH. In order to explore folate-mediated drug delivery, a partial total synthesis of folic acid is performed in order to selectively conjugate the ifosphamide analogs to the $\gamma$-carboxylate. The key step in this synthesis is the selective functionalization of glutamic acid which was achieved through the intermediacy of an oxazolidinone. Coupling between the functionalized glutamate and pteroic acid derivatives was achieved using the Rosowsky coupling technology and pteroyl azide. Several of the drug intermediates showed outstanding biological activity in three cell lines.
Degree
Ph.D.
Advisors
Fuchs, Purdue University.
Subject Area
Organic chemistry|Pharmaceuticals
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