Enantioselective total syntheses of manzamine A and related alkaloids
Enantioselective total syntheses of manzamine A and related alkaloids
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DOI：
10.1021/ja0202964
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发表时间：
2002-07-24
影响因子：
15
通讯作者：
Martin, SF
中科院分区：
文献类型：
--
作者：
Humphrey, JM;Liao, YS;Martin, SF
作为进行复杂manzamine生物碱的全合成的前奏，进行了一系列的模型研究，以建立N-酰化乙烯基脲与三烯底物17 a，B，28 a，B和34的分子内[4 + 2]环加成的范围和限制。这些实验清楚地表明，内部双键的几何形状和二烯部分上吸电子基团的存在对于所需环加合物的容易和立体选择性形成是必不可少的。然后，通过采用会聚策略完成了对映选择性合成manzamine生物碱ircinol A（75）、ircinal A（5）和manzamine A（1），该策略的特征在于新颖的多米诺Stille/Diels-Alder反应以构建这些生物碱中包含的三环ABC环核。因此，容易获得的手性二氢吡咯58首先在单一化学操作中转化为关键的三环中间体60。然后使用两个闭环复分解反应形成13元环和8元环，得到Z-72和74，后者通过间苯二酚A（75）迅速加工成间苯二酚A（5）。按照文献先例，将由此获得的合成物5转化为曼扎胺A（1）。从市售的起始原料进行的这种简明的手性A合成需要总共24个操作，最长的线性序列为21个步骤。
As a prelude to undertaking the total syntheses of the complex manzamine alkaloids, a series of model studies were conducted to establish the scope and limitations of intramolecular [4 + 2] cycloadditions of N-acylated vinylogous ureas with the trienic substrates 17a,b, 28a,b, and 34. These experiments clearly demonstrated that the geometry of the internal double bond and the presence of an electron-withdrawing group on the diene moiety were essential for the facile and stereoselective formation of the desired cycloadducts. The enantioselective syntheses of the manzamine alkaloids ircinol A (75), ircinal A (5), and manzamine A (1) were then completed by employing a convergent strategy that featured a novel domino Stille/Diels-Alder reaction to construct the tricyclic ABC ring core embodied in these alkaloids. Thus, the readily accessible chiral dihydropyrrole 58 was first converted in a single chemical operation into the key tricyclic intermediate 60. Two ring-closing metathesis reactions were then used to form the 13- and 8-membered rings leading to Z-72 and 74, the latter of which was quickly elaborated into ircinal A (5) via ircinol A (75). The synthetic 5 thus obtained was converted into manzamine A (1) following literature precedent. This concise synthesis of ircinal A required a total of 24 operations from commercially available starting materials with the longest linear sequence being 21 steps.