生物碱 (-)-phalarine 的合成研究

In 1999, Colegate and co-workers reported the isolation and structure elucidation of a novel furanobisindole alkaloid from the perennial grass P arundinacea named Phalarine. Its structure, as determined through intensive NMR studies, encompasses a novel furanobisindole framework featuring a unique propeller-like motif that different with other furanobisindole alkaloids. The critical chiral center was introduced via an organocatlyzed Michael addition, then deprotection of methyl group followed by a lewis acid-catalyzed intramolecular oxa-Michael addition was used to install the furoindole framework. Finally, reductive cyclization of cyanogroup with aldehyde was employed to construct the Phalarine skeleton, and further functional-group interconversion would finish the total synthesis of (-)-phalarine.

(-)-phalarine是Colegate小组从牧草Phalaris coerulescens中分离得到的吲哚并呋喃类生物碱。澳大利亚科学家为了探索对牲畜有害的牧草成分，优化牧场资源，从Phalaris coerulescens中分离出一种结构独特的生物碱(-)-phalarine，其骨架连接与其它吲哚并呋喃类生物碱不同。本课题设计了一条合成策略，通过最初的Strecker反应构筑Michael加成前体，然后引入炔丙醛片段，通过有机催化的Michael加成构筑吲哚，并引入关键手性中心。再通过Lewis催化的甲基脱保护原位氧杂Michael加成构筑Phalarine的吲哚并呋喃体系，最终通过还原胺化构筑Phalarine骨架并完成全合成

(-)-phalarine是Colegate小组从牧草Phalaris coerulescens中分离得到的吲哚并呋喃类的生物碱。澳大利亚科学家为了探索牧草中对牲畜有害的成分，优化牧场资源，从Phalaris coerulescens中分离出对牲畜有害的一种成分，其结构是一种独特的吲哚并呋喃结构的生物碱(-)-phalarine，(-)-phalarine具有扇形的[4.3.3.0]三环骨架连接，并且与其它已经发现的吲哚并呋喃生物碱不同，Phalarine具有反式并环的连接方式。我们设计了一条合成思路，通过最初的Strecker反应构筑Michael加成前体，然后引入炔丙醛片段，再通过有机催化的Michael加成构筑吲哚，并且构筑氮杂季碳，再通过Lewis催化的甲基脱保护原位氧杂Michael加成构筑Phalarine的吲哚并呋喃体系，最终通过对氰基和酯基的还原环化构筑整个Phalarine分子骨架，后续经过几步简单官能团转化完成Phalarine不对称合成