Synthesis of a regioisomeric analogue of the 3C-protease inhibitor thysanone via a Hauser annulation strategy
Synthesis of a regioisomeric analogue of the 3C-protease inhibitor thysanone via a Hauser annulation strategy
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DOI：
10.1016/j.tet.2006.11.046
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发表时间：
2007-01-22
期刊：
影响因子：
2.1
通讯作者：
Woodgate, Paul D.
中科院分区：
文献类型：
--
作者：
Brimble, Margaret A.;Houghton, Scott I.;Woodgate, Paul D.
豪瑟环化3-氰基-5，7-二甲氧基-（3 H）-异苯并呋喃-1-酮4与丙烯酸乙酯作为一种方法，以获得活化萘醌3，一个关键的中间体，用于合成噻酮1，被证明是不可靠的。与此相反，区域异构体3-氰基-4，6-二甲氧基-（3 H）-异苯并呋喃-1-酮13与丙烯酸乙酯的豪瑟环化反应在氧化初始二羟基萘16后容易地进行，得到乙基5，7-二甲氧基-1，4-萘醌12。萘醌12的烯丙基化，然后还原甲基化和Wacker氧化，得到酮11，其经历CBS还原成（2'S）-醇19，然后环化成内酯20。还原内酯，然后氧化去甲基，得到（1 S，3S）-6，8-二甲氧基-1-羟基-3-甲基吡喃并[2，3-c]-1，4-萘醌22，3C-蛋白酶抑制剂噻酮1的区域异构类似物。(c)2006爱思唯尔有限公司保留所有权利。
Hauser annulation of 3-cyano-5,7-dimethoxy-(3H)-isobenzofuran-1-one 4 with ethyl acrylate as a method to access activated naphthoquinone 3, a key intermediate for the synthesis of thysanone 1, proved unreliable. In contrast to this, Hauser annulation of regioisomeric 3-cyano-4,6-dimethoxy-(3H)-isobenzofuran-1-one 13 with ethyl acrylate proceeded readily affording ethyl 5,7-dimethoxy-1,4-naphthoquinone 12, after oxidation of the initial dihydroxynaphthalene 16. Allylation of naphthoquinone 12 followed by reductive methylation and Wacker oxidation afforded ketone 11 that underwent CBS reduction to (2'S)-alcohol 19 followed by cyclisation to lactone 20. Reduction of the lactone followed by oxidative demethylation afforded (1S,3S)-6,8-dimethoxy-1-hydroxy-3-methylpyrano[2,3-c] -1,4-naphthoquinone 22, a regioisometic analogue of the 3C-protease inhibitor thysanone 1. (c) 2006 Elsevier Ltd. All rights reserved.