虎皮楠生物堿daphenylline的首次全合成報(bào)告

摘 要：虎皮楠生物堿（Daphniphyllum alkaloid）是一大類從虎皮楠科植物中分離的具有化學(xué)、生物和生物合成等多方面研究意義的天然產(chǎn)物。李昂等發(fā)展了一條19步的合成路線，從4個(gè)結(jié)構(gòu)簡(jiǎn)單的片段出發(fā)，反應(yīng)完成了daphenylline的首次不對(duì)稱全合成（Nature Chemistry 2013，5，679-684）。該合成主要的碳-碳鍵形成反應(yīng)包括：金（I）催化的6-exo-dig炔烴環(huán)化反應(yīng)以構(gòu)建[3.3.1]橋環(huán)體系、分子內(nèi)Michael加成反應(yīng)以構(gòu)建吡咯烷結(jié)構(gòu)、光引發(fā)的烯烴異構(gòu)化/6π電環(huán)化串聯(lián)反應(yīng)和隨后的氧化芳構(gòu)化反應(yīng)以構(gòu)建四取代苯環(huán)結(jié)構(gòu)、自由基環(huán)化反應(yīng)以構(gòu)建七元環(huán)結(jié)構(gòu)。這一工作將促進(jìn)下一步的活性—靶點(diǎn)—機(jī)制的研究工作。

關(guān)鍵詞：虎皮楠生物堿 全合成 電環(huán)化

Abstract： The Daphniphyllum alkaloids are a large class of natural products isolated from a genus of evergreen plants widely used in Chinese herbal medicine. They display a remarkable range of biological activities， including anticancer， antioxidant， and vasorelaxation properties as well as elevation of nerve growth factor. Daphenylline is a structurally unique member among the predominately aliphatic Daphniphyllum alkaloids， and contains a tetrasubstituted arene moiety mounted on a sterically compact hexacyclic scaffold. Herein， we describe the first total synthesis of daphenylline. A gold-catalysed 6-exo-dig cyclization reaction and a subsequent intramolecular Michael addition reaction were exploited to construct the bridged 6，6，5-tricyclic motif of the natural product at an early stage， and the aromatic moiety was forged through a photoinduced olefin isomerization/6p-electrocyclization cascade followed by an oxidative aromatization process.

Key Words： Daphniphyllum alkaloids； Total synthesis； Electrocyclization

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