Studies on the synthesis of (-)-gymnodimine. Subunit synthesis and coupling.
Studies on the synthesis of (-)-gymnodimine. Subunit synthesis and coupling.
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(-)-裸二胺的合成研究。
DOI：
10.1021/jo062396o
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Wang,Guoqiang
中科院分区：
文献类型：
--
作者：
White,JamesD;Quaranta,Laura;Wang,Guoqiang
合成了海藻毒素（−）-裸藻亚胺的两个主要亚基。三取代的四氢呋喃代表毒素的C10−C18通过高度立体选择性的碘介导的环化带有双-2，6-二氯苄基（DCB）醚的无环烯烃来制备。在此过程中形成的顺式-2，5-二取代的四氢呋喃符合Bartlett和Rychnovsky提出的DCB基团的立体定向效应。通过1，2，3-三取代的二烯与从Meldrum酸得到的对称亲二烯体的Diels−桤木环加成反应，合成了一个对应于裸甲亚胺C1−C8，C19−C24部分的环己烯亚基。环加合物中羰基的分化是通过与相邻醇的分子内反应形成γ-内酯来实现的。两个亚基在C18−C19的连接是通过使用B-烷基铃木偶联完成的，其中从环己烯结构域的侧链烯基链制备的硼烷与连接在四氢呋喃部分的C16的（E）-碘代烯烃反应。随后的转化将官能团定位在偶联产物中，用于未来的大环化事件，该大环化事件将关闭裸甲亚胺的15元环。
Two principal subunits of the marine algal toxin (−)-gymnodimine were synthesized. A trisubstituted tetrahydrofuran representing C10−C18 of the toxin was prepared via a highly stereoselective iodine-mediated cyclization of an acyclic alkene bearing a bis-2,6-dichlorobenzyl (DCB) ether. The formation of a cis-2,5-disubstituted tetrahydrofuran in this process conforms to a stereodirecting effect by the DCB group proposed by Bartlett and Rychnovsky. A cyclohexene subunit corresponding to the C1−C8, C19−C24 portion of gymnodimine was synthesized via Diels−Alder cycloaddition of a 1,2,3-trisubstituted diene to a symmetrical dienophile obtained from Meldrum's acid. Differentiation of carbonyl groups in the cycloadduct was made by an intramolecular reaction with a neighboring alcohol to form a γ-lactone. Linkage of the two subunits at C18−C19 was accomplished by using a B-alkyl Suzuki coupling in which a borane prepared from the pendent alkenyl chain of the cyclohexene domain was reacted with the (E)-iodoalkene attached at C16 of the tetrahydrofuran sector. Subsequent transformations positioned functional groups in the coupled product for a future macrocyclization event that would close the 15-membered ring of gymnodimine.