Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A.
Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A.
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佛波唑A全合成立体控制烯丙基化反应的研究。
DOI：
10.1073/pnas.0402477101
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发表时间：
2004
影响因子：
11.1
通讯作者：
Reeves,JonathanT
中科院分区：
文献类型：
--
作者：
Williams,DavidR;Kiryanov,AndreA;Emde,Ulrich;Clark,MichaelP;Berliner,MartinA;Reeves,JonathanT
完成了高效抗癌剂(+)-呋喃唑甲的高度收敛全合成。组装了四个组分(-)，并考虑了绝对和相对立体化学的控制。迭代不对称烯丙化方法解决了制备C3-C19组分的2，6-顺式和2，6-反式四氢吡喃环的关键立体化学特征。立体控制的不对称烯丙基化过程也用于C28-C41片段的开发。本文报道了α-碘甲基恶唑及其相关的噻唑类化合物的新型Barbier偶联反应。组分4和5的聚合组装特征是通过分子内捕获具有高表面选择性的烯丙基阳离子中间体形成完全取代的C22-C26吡喃，进一步的努力导致TOE-C19/C20烯化。合成的最终结果是使用改进的Julia烯化反应连接C42-C46链段，随后通过安装(Z)-C2/C3α，β-不饱和内酯进行后期大环化。
A highly convergent total synthesis of the potent anticancer agent (+)-phorboxazole A is accomplished. Four components (–) are assembled with considerations for control of absolute and relative stereochemistry. Iterative asymmetric allylation methodology addresses key stereochemical features in the preparation of the 2,6-cis- and 2,6-trans-tetrahydropyranyl rings of the C3–C19 component . The stereocontrolled asymmetric allylation process is also used for development of the C28–C41 fragment . Novel Barbier coupling reactions of α-iodomethyl oxazoles and related thiazoles are described with samarium iodide. The convergent assembly of components 4 and 5 features formation of the fully substituted C22–C26 pyran by intramolecular capture of an allyl cation intermediate with high facial selectivity, and further efforts lead toE-C19/C20 olefination. The synthesis culminates with use of a modified Julia olefination for attachment of the C42–C46 segment and subsequent late-stage macrocyclization by installation of the (Z)-C2/C3 α,β-unsaturated lactone.