Enantioselective total synthesis of octalactin a using asymmetric aldol reactions and a rapid lactonization to form a medium-sized ring
Enantioselective total synthesis of octalactin a using asymmetric aldol reactions and a rapid lactonization to form a medium-sized ring
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DOI：
10.1002/chem.200500417
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发表时间：
2005-11-04
影响因子：
4.3
通讯作者：
Ibuka, R
中科院分区：
文献类型：
--
作者：
Shiina, I;Hashizume, M;Ibuka, R
Octalactin A是一种含有八元内酯结构的抗肿瘤药物，在手性Sn-II络合物的催化下，通过选择性的烯醇化硅酯与非手性醛的羟醛缩合反应，立体选择性地合成了该化合物。以2-甲基-6-硝基苯甲酸酐（MNBA）和催化量的4-（二甲氨基）吡啶（DMAP）或4-（二甲氨基）吡啶氧化物（DMAPO）为原料，通过一种新的快速混合酸酐内酯化反应，有效地构建了中等大小的内酯部分。仅使用5摩尔%的DMAP或2摩尔%的DMAPO就迅速促进了octalactin的中等大小环的形成，证明了新的内酯化方案的显著效率。
Octalactin A, an antitumor agent containing an eight-membered lactone moiety, has been stereoselectively prepared by means of enantioselective aldol reactions of selected silyl enolates with achiral aldehydes, promoted by a chiral Sn-II complex. The medium-sized lactone part was effectively constructed by way of a new and rapid mixed-anhydride lactonization using 2-methyl-6-nitrobenzoic anhydride (MNBA) with a catalytic amount of 4- (dimethylamino)pyridine (DMAP) or 4-(dimethylamino)pyridine I-oxide (DMAPO). The use of only 5 mol % of DMAP or 2 mol % of DMAPO rapidly promoted formation of the medium-sized ring of the octalactin, demonstrating the remarkable efficiency of the new lactonization protocol.