Synthesis and antimalarial activity of heteroatom-containing bicyclic endoperoxides
Synthesis and antimalarial activity of heteroatom-containing bicyclic endoperoxides
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DOI：
10.1016/s0040-4020(96)00975-1
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发表时间：
1997-01-06
期刊：
影响因子：
2.1
通讯作者：
Shapiro, TA
中科院分区：
文献类型：
--
作者：
Posner, GH;Gonzalez, L;Shapiro, TA
Mechanism-based design and short syntheses involving novel Tebbe methylenations of n-heteroatom-substituted ketones led to preparation of heteroatom-containing bicyclic endoperoxides 4-6. The crucial final photo-oxygenative cyclization step succeeded only when the intermediate 1,6-dienes carried anisyl but not phenyl substitutents. Distinguishing between endoperoxide and cyclobutane cyclization products was achieved reliably by C-13 NMR spectroscopy. Antimalarial testing of endoperoxides 4-6 in vitro showed them to have only weak activities (IC50 = 500-1100 nM). Ferrous bromide-induced reductions of sulfonamide endoperoxides 4, although forming the expected hydroxylated ether and ring-contracted products 7 and 8, caused virtually no rearrangement of hexamethyl Dewar benzene; therefore, the intermediacy of any oxidatively damaging high-valent iron-axe intermediate appears unlikely. Copyright (C) 1996 Elsevier Science Ltd
