Synthetic studies towards garsubellin A: synthesis of model systems and potential mimics by regioselective lithiation of bicyclo[3.3.1]nonane-2,4,9-trione derivatives from catechinic acid
Synthetic studies towards garsubellin A: synthesis of model systems and potential mimics by regioselective lithiation of bicyclo[3.3.1]nonane-2,4,9-trione derivatives from catechinic acid
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DOI：
10.1039/b704311b
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Wilson, Claire
中科院分区：
文献类型：
--
作者：
Ahmad, Nadia M.;Rodeschini, Vincent;Wilson, Claire
桥头锂化已成功地在衍生自儿茶酸的底物上进行，儿茶酸具有garsubellin A中存在的核心双环[3.3.1]壬烷-1，3，5-三酮结构。使用外部淬灭方法，各种亲电试剂已被纳入在C-5桥头位置在一个一步的过程中，似乎是敏感的取代模式上的双环系统。通过将所用碱从LDA改变为LTMP，实现了在C-3sp（2）中心的区域选择性锂化。通过桥头取代引入异戊烯基取代基后，类似于garsubellin A中的THF环的环化可以通过环氧化开环序列进行。氧化修饰儿茶酸核心的儿茶酚取代基的阳离子可以得到具有粘康酸、邻醌或呋喃2-羧酸侧链的体系。
Bridgehead lithiations have successfully been carried out on substrates derived from catechinic acid, which possess the core bicyclo[3.3.1] nonane-1,3,5-trione structure present in garsubellin A. Using an external quench method, various electrophiles have been incorporated at the C-5 bridgehead position in a one-step process that appears to be sensitive to the substitution pattern on the bicyclic system. Regioselective lithiation at the C-3 sp(2) centre was achieved by changing the base used from LDA to LTMP. Following the introduction of a prenyl substituent by bridgehead substitution, annulation of a THF ring, analogous to that in garsubellin A, was possible via an epoxidation-ring opening sequence. Oxidative modi. cation of the catechol substituent of the catechinic acid core was possible to give systems with muconic acid, ortho-quinone or furan 2-carboxylic acid side chains.