Total syntheses of epothilones B and D
Total syntheses of epothilones B and D
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DOI：
10.1021/jo0007480
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发表时间：
2000-11-03
影响因子：
3.6
通讯作者：
Öhler, E
中科院分区：
文献类型：
--
作者：
Mulzer, J;Mantoulidis, A;Öhler, E
以光学纯的（S）-苹果酸和（R）-3-羟基-2-甲基丙酸甲酯为起始原料，全合成了微管稳定抗肿瘤药物埃坡霉素B和D。通过偶联三个片段C1-C6（片段D）、C7-C10（片段C）和C11-C21（片段B），合成高度收敛。关键步骤是两个立体选择性Wittig型烯化反应生成12，13-和16，17-双键，对映选择性Mukaiyama羟醛加成合成片段D，以及砜阴离子烯丙基碘烷基化连接片段B和C。最后通过羟醛加成将片段D连接到B + C片段上。
Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.