Synthesis and antimalarial activity of heteroatom-containing bicyclic endoperoxides

被引：53

作者：

Posner, GH ^{[1
]}

Gonzalez, L ^{[1
]}

Cumming, JN ^{[1
]}

Klinedinst, D ^{[1
]}

Shapiro, TA ^{[1
]}

机构：

[1] JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21205

来源：

TETRAHEDRON | 1997年 / 53卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S0040-4020(96)00975-1

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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

引用

页码：37 / 50

页数：14

共 45 条

[1] 1,2,4-TRIOXEPANS - SYNTHESIS AND MASS-SPECTRAL BEHAVIOR [J].