(±)-Paniculidine B, (±)-Paniculidine C, (±)- Festuclavine與(±)-Pibocin B之合成研究

Abstract

本論文內容共分兩個部分:第一部分為天然物(±)-paniculidine B和(±)-paniculidine C的全合成，第二部分則為天然物(±)-festuclavine與(±)-pibocin B的合成研究。

第一部分:利用市售的吲哚21為起始物，透過Tamaru丙烯基化反應選擇性的在吲哚C-3位置上引入丙烯基得到化合物20，接著將化合物20還原並透過Somei氧化製備化合物18，再利用格拉布催化劑與甲基丙烯醇進行烯烴交叉複分解得到化合物17，最後以鈀碳催化劑對烯烴氫化得到天然物(±)-paniculidine B (1)。另一方面化合物20也可以直接與甲基丙烯醇進行烯烴交叉複分解得到化合物22，氫化後得到另一個天然物(±)-paniculidine C (2)。

第二部分:我們同樣參考Tamaru丙烯基化反應利用化合物45製備出化合物82，接著透過銅催化芬克爾斯坦反應與保護基修飾得到化合物117，在確認化合物117可透過自由基環化得到化合物118a後，我們探討該成環反應運用在合成天然物(±)-festuclavine (28)與(±)-pibocin B (32)的可行性，利用化合物117與化合物119利用格拉布催化劑進行烯烴交叉複分解得到化合物120，再藉由光延反應置換成化合物121，化合物121與不同的自由基起始劑與氫提供者測試關鍵的自由基環化級聯反應。另一方面我們也合成117、133、135和137這四個化合物，並與對甲苯磺醯胺化合物125進行烯烴交叉複分解得到化合物126、化合物131、化合物134與化合物136，並探討藉由這些前驅物利用鈀催化級聯反應建立(±)-festuclavine (28)與(±)-pibocin B (32)天然物骨架之合成研究。

This thesis is composed of two parts under a common theme of alkaloid synthesis. The first part describes the total syntheses of (±)-paniculidine B (1) and (±)-paniculidine C (2); the second part details our effort toward the synthesis of (±)-festuclavine and (±)-pibocin B.

In the first part we used commercial available indole (21) as starting material, and selectively introduced an allyl group at the C-3 position of indole via the Tamaru allylation. Reduction of 20, followed by Somei oxidation afforded compound 18. The olefin cross metathesis between methallyl alcohol provided compound 17. The hydrogenation of 17 in THF with palladium on carbon accomplished the total synthesis of (±)-paniculidine B (1). On the other hand, compound 22 can also be synthesized from 3-allylindole 20 via the similar sequence to obtain (±)-paniculidine C (2).

In the second part, compound 82 was synthesized from commercial available compound 45 through Tamaru allylation. Subsequent iodination by copper-catalyzed Finkelstein reaction and tosylation afforded compound 117. A model study revealed that 118a could be prepared via a 6-endo-trig free-radical cyclization. Next we investigated the feasibility of constructing the tetracyclic framework of ergot alkaloids, namely (±)-festuclavine (28) and (±)-pibocin B (32), via the free-radical cascade cyclization. In addition, compounds 126, 131, 134 and 136 could also be obtained by conducting olefin-cross metathesis of 125 with the corresponding substituted indoles and an indoline. Finally, the palladium-catalyzed cascade cyclization was systematically investigated as an alternative strategy to construct the ergot alkaloid skeleton.