Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol
Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol
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DOI：
10.1002/chem.200701386
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Katoh, Tadashi
中科院分区：
文献类型：
--
作者：
Sakurai, Junji;Oguchi, Takamasa;Katoh, Tadashi
以(+)-5-甲基-威兰-米谢尔酮10为起始原料，以(+)-5-甲基-威兰-米歇酮10为起始原料，高效地合成了具有重要生物意义和独特结构的海洋天然产物香豆素(1)、香豆素(2)、新香豆素(3)、新香豆素(4)和金香兰素(5)。合成过程包括以下关键步骤：1)BF(3)中心点(2)O诱导2和4重排/环化反应，高产率地得到完全立体选择性的5(2-和4-)；Ii)酚类化合物6和8的Salcomine战略氧化反应，以得到相应的醌1和3(6-gt；1和8-gt；3)；以及iii)10与溴11的Birch还原烷基化反应，以构建所需的碳骨架12(10+11->；12)。化合物1-5对人组织细胞淋巴瘤细胞U937的体外细胞毒试验确定了细胞毒作用的顺序(3>；1>；5>；2>；4)和一些构效关系的新方面。
Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)center dot Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 -> 5 and 4 -> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 -> 1 and 8 -> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 -> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.