Total synthesis of piericidin A1 and B1 and key analogues
Total synthesis of piericidin A1 and B1 and key analogues
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DOI：
10.1021/ja0632862
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发表时间：
2006-09-13
影响因子：
15
通讯作者：
Boger, Dale L.
中科院分区：
文献类型：
--
作者：
Schnermann, Martin J.;Romero, F. Anthony;Boger, Dale L.
描述了杀粉蝶菌素A1和B1的全合成及其延伸到制备一系列关键类似物的全部细节，包括ent-杀粉蝶菌素A1（ent-1）、4’-脱羟基杀粉蝶菌素A1（58）、5’-脱甲基杀粉蝶菌素A1（73）、4’-脱羟基-5’-脱甲基杀粉蝶菌素A1（75）和相应的类似物51、59、76，和带有简化的法尼基侧链的77。这些关键类似物的评价，沿着从他们的进一步官能化衍生的那些，允许扫描的关键结构特征提供新的见解的作用中发现的取代基的吡啶核心以及侧链。一个战略性的后期阶段杂苄基Stille交叉偶联反应的吡啶核心与充分阐述的侧链允许随时访问的类似物，其中每一半的分子可以系统地和不同的修改。吡啶核的组装是通过N-磺酰基-1-氮杂丁二烯的反电子需求Diels-Alder反应进行的，而侧链合成的关键要素包括反选择性不对称羟醛醇以安装C9和C10的相对和绝对立体化学（对于天然和ent-1）和用于形成C5-C6反式双键的改进的Julia烯化，侧链的会聚组装。
Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation of a series of key analogues are described including ent-piericidin A1 (ent-1), 4'-deshydroxypiericidin A1 (58), 5'-desmethylpiericidin A1 (73), 4'-deshydroxy-5'-desmethylpiericidin A1 (75), and the corresponding analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues, along with those derived from their further functionalizations, permitted a scan of the key structural features providing new insights into the role of the substituents found in both the pyridyl core as well as the side chain. A strategic late stage heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain permitted ready access to the analogues in which each half of the molecule could be systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electron demand Diels-Alder reactions of N-sulfonyl-1-azabutadienes, while key elements of side chain syntheses include an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry (for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chains.