(±)-Simonsol C之全合成研究

Total Synthesis of (±)-Simonsol C

張喻晴(Yu-Ching Chang)

指導教授 ： 吳彥谷

國立交通大學/理學院/應用化學系所/碩士(2020年)

摘要

在2013年天然物simonsol C由Wang等人從西蒙氏八角(Illicium simonsii)中萃取分離出來，其具有四氫二苯并呋喃(tetrahydrodibenzo[b,d]furan)的骨架以及和那維定(narwedine)有極為相似的ABC環結構，那維定是具有生物活性的加蘭他敏(galanthamine)的中間體。近年來，加蘭他敏主要用來抑制乙醯膽鹼酯 酶(這個作用可以治療輕度到中度的阿茲海默氏病，也就是所謂的失智症。
合成路徑有遇到的挑戰是在反應中確保三個烯丙基的雙鍵不被重排。在我們研究中，我們歷經了七個步驟來完成simonsol C的全合成。其中，建構simonsol C中間的呋喃環是透過運用環狀插烯酯(cyclic vinylogous ester)和溴化芳基(aryl bromide)進行鈀金屬催化的α芳基化反應，進而產生分子間的碳-碳鍵；再者，我們選擇藉由硫醇試劑對芳基甲醚進行去甲基保護，可以促使麥可加成反應(Michael addition)，最後形成分子內的碳-氧鍵。

關鍵字

天然物全合成 ； α 芳基化反應 ； 西蒙氏八角 ； 四氫二苯并呋喃 ； 麥可加成反應

並列摘要

Simonsol C was isolated from the Illicium simonsii by Wang in 2013. This natural product possesses the framework of tetrahydrodibenzo[b,d]furan and it is highly similar to the ABC-ring structure of narwedine, which is an immediate precursor to galanthamine. Recently, galanthamine plays an important role as an inhibitor of acetylcholinesterase (AChE), which is a good treatment for mild to moderate symptoms of Alzheimer’s disease (AD).
Total synthesis of simonsol C is full of numerous challenges, especially maintaining the correctness of positions of the three allyl moieties in the reaction. In our study, we experienced a 7-step sequence to reach the racemic total synthesis of simonsol C. The central furan ring of simonsol C was constructed through Pd-catalyzed α-arylation reaction with cyclic vinylogous ester and aryl bromide to generate intermolecular C-C bond, and we selected demethylation of aryl methyl ether with thiol reagent to promote oxa-Michael addition to form intramolecular C-O bond.

並列關鍵字

Natural product total synthesis ； α-arylation reaction ； Illicium simonsii ； tetrahydrodibenzo[b,d]furan ； Michael addition

參考文獻

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