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

被引：144
作者：
Boger, DL
Soenen, DR
Boyce, CW
Hedrick, MP
Jin, Q
机构：
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
来源：
JOURNAL OF ORGANIC CHEMISTRY | 2000年 / 65卷 / 08期
关键词：
D O I：
10.1021/jo9916535
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
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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页码：2479 / 2483
页数：5
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