Stereocontrolled and convergent total synthesis of amphidinolide T3
Stereocontrolled and convergent total synthesis of amphidinolide T3
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DOI：
10.1021/jo0605086
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发表时间：
2006-06-09
影响因子：
3.6
通讯作者：
Zhao, Gang
中科院分区：
文献类型：
--
作者：
Deng, Li-Sheng;Huang, Xiao-Ping;Zhao, Gang
报道了立体控制和收敛全合成两性内酯T3的方法。构建了一种逆合成方案，使易得的和对映体相关的化合物被识别为全合成两性内酯T3的起始原料。因此，两个关键的构建块6和7被定义为亚目标，并以光学活性形式合成。C_1-C_(12)片段6以市售D-谷氨酸或其合成等价物(R)-5-羟甲基四氢呋喃-2-酮16为起始原料，以高度非对映选择性的不对称烯丙基化为关键步骤。C13-C21片段7通过链段10和碘11的二硫烷偶联、随后的去保护和Petsis烯化反应高效地合成。最终，片断醛6和二硫代烷7的组装以及C-C键的形成、两步氧化还原序列、选择性大内酯和官能团的转换提供了收敛的全合成和形式合成两性内酯T3和T4的方法，该方法也提供了一种灵活实用的合成两性内酯T大内酯的方法。
Stereocontrolled and convergent total synthesis of amphidinolide T3 has been described. A retrosynthetic scheme was constructed that led to the recognition of readily available and enantiomerically related compounds as starting materials for the total synthesis of amphidinolide T3. Thus, the two key building blocks 6 and 7 were defined as subtargets and synthesized in optically active forms. The C1-C12 fragment 6 was derived from commercially available D-glutamic acid or its synthetically equivalent (R)-5-hydroxymethyltetrahydrofuran-2-one 16 as starting material involving highly diastereoselective asymmetric allylation as a key step. The C13-C21 fragment 7 was efficiently synthesized in high yield through the dithiane coupling of the segment 10 and iodide 11, followed by subsequent deprotection and Petasis olefination. Eventually, assembly of the fragment aldehyde 6 and dithiane 7 along with C-C bond formation, a two-step oxidation-reduction sequence, selective macrolactonization, and functional transformation furnished the convergent total and formal synthesis of amphidinolide T3 and T4, and this approach also provides a flexible and practical synthesis of amphidinolide T macrolides.