1. Advancements in the Synthesis of Mutual Anticancer Prodrugs

Eric Dobias Thomas More College, David Kelley Thomas More College
Faculty Sponsor(s): Daniel Esterline Thomas More College
Mutual prodrugs, where two different anti-cancer drugs are attached to a linkage molecule by labile linkages, have revolutionized the field of medicinal chemistry with their renown benefits such as therapeutic pharmacokinetics, selective absorption, and decrease in toxicity to healthy tissues. This research was designed to expand upon a reported mutual anticancer prodrugs, “N- (1-β-D-Arabinofuranosylcystosyl)succinamic Acid” and 5-[(1-β -D-Arabinofuranosylcytosoyl)methyl Ester”, by investigating various linkage lengths between the Cytarabine and 5-Flourouracil moieties, as well as structural additions to the linkage chain itself. The synthesis of these mutual prodrugs includes a seven-step process, starting with the nucleophilic addition of a benzyl alcohol to a cyclic anhydride as seen in the reaction schematic and eventually leads to the direct nucleophilic addition of the two active drugs through ester/amide bonds. So far, various steps have been achieved through the use of the following starting materials; Succinic anhydride, itaconic anhydride, glutaric anhydride, p-bromobenzyl alcohol, benzyl alcohol, and pentafluorobenzylalcohol. Gas-Chromatography-Mass Spectroscopy (EI) and Proton Nuclear Magnetic Resonance Spectroscopy were utilized for structural determination. Final yields cannot yet be determined as residual solvents and unreacted starting materials were detected by GC-MS and (_^1)HNMR.
Chemistry
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Irwin Library 1st Floor