PROGRESS TOWARD THE TOTAL SYNTHESIS OF 14-ISOAZACAMPTOTHECIN AND SYNTHESIS OF SUBSTITUTED QUINOLINES.

Abstract

BORI, IBRAHIM DANLAMI. Progress Toward the Total Synthesis of 14-Isoazacamptothecin, and Synthesis of Substituted Quinolines. (Under the direction of Professor Daniel Lee Comins.)

Studies were conducted with the purpose of completing the first total synthesis of 14-isoazacamptothecin. During the courses of this endeavor, new insights into pyridine chemistry were uncovered. It was demonstrated for the first time that C-4 substitution of 2,5-dibromopyridine via C-4 lithiation is indeed possible. New reactions in heterocyclic chemistry, namely (a) “Halogen Dance-Lithium Migration-Halogen Dance†or “Lithium Migration-Halogen Dance†and (b) Double Halogen Dance†were discovered to have taken place as explanations for the observation of unexpected products. Synthetic methods toward the synthesis of new quinoline analogs using readily available and inexpensive starting materials were developed. Although the initial inspirational target of the project was the AB ring fragment of CPT analogs, new techniques and methods were developed that would be useful in far reaching applications such as in the synthesis of clinically useful compounds and natural products containing a quinoline ring in the parent structure.