Stereocontrolled total syntheses of meso-chimonanthine and meso-calycanthine via a novel samarium mediated reductive dialkylation
Stereocontrolled total syntheses of meso-chimonanthine and meso-calycanthine via a novel samarium mediated reductive dialkylation
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DOI：
10.1021/ja961757m
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发表时间：
1996-08-28
影响因子：
15
通讯作者：
Overman, LE
中科院分区：
文献类型：
--
作者：
Link, JT;Overman, LE
十二环多吲哚啉生物碱Psycholeine（1）是由Sévenet及其同事于1992年从新喀里多尼亚植物Psychotria oleoides中分离出来的。据报道，这种新的天然产物是生长抑素受体家族的第一种非肽拮抗剂，因此具有潜在的治疗意义。2 Psycholeine（1），[R] 20 D-150，在结构上是显著的，其具有中心非手性六环核，该中心非手性六环核被两个具有相同绝对手性的吡咯并吲哚啉装饰。在meso-calycanthine（3）中也发现了非手性六环单元，其通过双（吡咯并吲哚啉）生物碱meso-chimonanthine（2）的酸催化重排获得。3在这篇通讯中，我们报道了第一个立体控制的全合成meso-chimonanthine（2）和meso-calycanthine（3），作为发展全合成psycholeine（1）策略的第一步。4以往的双（吡咯并吲哚啉）生物碱的合成工作主要通过羟吲哚（或色胺）的氧化二聚反应或3，3′-双（羟吲哚）的二烷基化反应来产生外消旋异构体。6我们预期meso-chimonanthine（2）可以由环己烯7构建，环己烯7是一种中间体，含有2和3中存在的两个关键季碳中心（方案1）。环己烯7是
The dodecacyclic polyindoline alkaloid psycholeine (1) was isolated from the New Caledonian plant Psychotria oleoides in 1992 by Sévenet and co-workers using a bioactivity-guided fractionation approach. 1 This novel natural product is reported to be the first non-peptide antagonist of the somatostatin family of receptors, and therefore is of potential therapeutic interest. 2 Psycholeine (1),[R] 20 D-150, is structurally remarkable having a central achiral hexacyclic core that is adorned with two pyrroloindolines of the same absolute chirality. The achiral hexacyclic unit also is found in meso-calycanthine (3), which is obtained by acid-catalyzed rearrangement of the bis (pyrroloindoline) alkaloid meso-chimonanthine (2). 3 In this communication, we report the first stereocontrolled total syntheses of meso-chimonanthine (2) and meso-calycanthine (3) as the initial step in the development of a strategy for the total synthesis of psycholeine (1). 4Past synthetic efforts directed toward bis (pyrroloindoline) alkaloids have produced predominantly the racemic isomers either by oxidative dimerization of oxindoles (or tryptamines) 3, 5 or from dialkylation of 3, 3′-bis (oxindoles). 6 We anticipated that meso-chimonanthine (2) could be constructed from cyclohexene 7, an intermediate that contains the two key quaternary carbon centers present in 2 and 3 (Scheme 1). Cyclohexene 7 was