Total Synthesis of Ningalin B Utilizing a Heterocyclic Azadiene Diels−Alder Reaction and Discovery of a New Class of Potent Multidrug Resistant (MDR) Reversal Agents
The Journal of Organic Chemistry2000Vol. 65(8), pp. 2479–2483
Citations Over TimeTop 10% of 2000 papers
Abstract
A concise, efficient approach to the total synthesis of ningalin B (1) based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine-->1,2,-diazine-->pyrrole) ideally suited for construction of the densely functionalized pyrrole core found in the natural product is detailed. Examination of the natural product and a number of synthetic intermediates revealed that while lacking inherent cytotoxic activity, many reverse the multidrug-resistant (MDR) phenotype, resensitizing a human colon cancer cell line (HCT116/VM46) to vinblastine and doxorubicin at lower doses than the prototypical agent verapamil.
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