Regioselective quinazolinone-directed ortho lithiation of quinazolinoylquinoline: Practical synthesis of naturally occurring human DNA topoisomerase I poison luotonin A and luotonins B and E
Regioselective quinazolinone-directed ortho lithiation of quinazolinoylquinoline: Practical synthesis of naturally occurring human DNA topoisomerase I poison luotonin A and luotonins B and E
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DOI：
10.1021/jo040153v
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发表时间：
2004-06-25
影响因子：
3.6
通讯作者：
Argade, NP
中科院分区：
文献类型：
--
作者：
Mhaske, SB;Argade, NP
在邻基喹啉基团上的区域选择性的喹唑烷酮催化的邻位锂化合成了一种短、高效、实用的人DNA拓扑异构酶I毒物罗托宁A和洛托宁B和E。用原位生成的非亲核间苯基锂处理喹唑基喹啉5得到了所需的二锂中间体6，该中间体与甲醛反应后经Mitsunobu环闭合反应以很高的产率得到了洛托宁A(1a)。二锂中间体6与DMF反应，以81%的产率直接合成了罗汉甲素B(1b)。罗汉甲素B(1b)经对TSA/甲醇甲基化反应得到罗丹明E(1c)，产率为82%。
A regioselective quinazolinone-directed ortho lithiation on an adjacent quinoline moiety has been used as a key step for a short, efficient, and practical synthesis of the human DNA topoisomerase I poison luotonin A and luotonins B and E. The quinazolinoylquinoline 5 on treatment with in situ-generated nonnucleophilic mesityllithium furnished the desired dilithiated intermediate 6, which on treatment with formaldehyde followed by Mitsunobu ring closure reaction gave luotonin A (1a) in very good yield. The reaction of dilithiated intermediate 6 with DMF directly furnished luotonin B (1b) in 81% yield. Luotonin B (1b) on methylation with p-TSA/methanol gave luotonin E (1c) in 82% yield.