Applications of a novel pyridine-forming reaction: The total syntheses of kuanoniamine D, dercitins, and lavendamycin methyl ester
Bishop, Michael Joseph
Ciufolini, Marco A.
Doctor of Philosophy
Several bioactive thiazolopyridoacridines of marine origin have been synthesized. Kuanoniamine D was synthesized in 18 steps from cyclohexanedione mono-ethyleneketal in 7.3% overall yield. The most potent member of the family, dercitin, was also synthesized from cyclohexanedione mono-ethyleneketal in 18 steps and 7.2% overall yield. Nordercitin was produced from the same starting material in 16 steps and 9.3% overall yield. This work also confirms the revision of the controversial structural assignments of dercitin and nordercitin. These efficient total syntheses include a new pyridine-forming sequence and a photochemical nitrene insertion as crucial steps. A novel approach to the streptonigrinoids, a family of potent antitumor antibiotics, is also described. An efficient formal total synthesis of the methyl ester of lavendamycin has been completed to demonstrate the usefulness of this approach. Key steps include a new pyridine-forming sequence and a thermolytic nitrene insertion to form a $\beta$-carboline. This formal synthesis is several steps shorter and an order of magnitude more productive than previously reported synthetic approaches.