Deng Li-Sheng, Huang Xiao-Ping, Zhao Gang
Laboratory of Modern Organic Synthetic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, 200032, PR China.
J Org Chem. 2006 Jun 9;71(12):4625-35. doi: 10.1021/jo0605086.
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.
已报道了两性霉素T3的立体控制和汇聚式全合成。构建了一种逆合成方案，该方案使人们认识到易于获得且对映体相关的化合物可作为两性霉素T3全合成的起始原料。因此，将两个关键结构单元6和7定义为子目标，并以光学活性形式合成。C1-C12片段6以市售的D-谷氨酸或其合成等效物（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不对称烯丙基化为关键步骤衍生而来。C13-C21片段7通过片段10与碘化物11的二硫烷偶联，随后进行脱保护和Petasis烯化反应，以高产率高效合成。最终，片段醛6和二硫烷7的组装以及碳-碳键的形成、两步氧化还原序列、选择性大环内酯化和官能团转化实现了两性霉素T3和T4的汇聚式全合成和形式合成，并且该方法还提供了一种灵活实用的两性霉素T大环内酯的合成方法。
