Indolo[2,3-a]quinolizidine 1 (Scheme 1) has an interesting history. First synthesized by Keufer in 1950, this tetracyclic amine was subsequently prepared by several others, only later to be discovered as a naturally occurring plant alkaloid from the New Guinea tree Dracontomelum mangiferum. This represents a rare case of a natural product being discovered after its synthesis. Several enantioselective syntheses established the S-configuration for 1, although the isolated alkaloid was found to be partially racemic. Other syntheses have been reported. The 10-bromo derivative (arborescidine A) was isolated in 1993 from the marine tunicate Pseudodistoma arborescens, and, accordingly, 1 has been named desbromoarborescidine A. Despite myriad syntheses of 1, we felt that none are suitable for a large-scale preparation that we required for a project in our laboratory. We now describe a simple and atom-economical synthesis of (±)-1 from tryptophan (2) and dihydropyran (3) (Scheme 1). A classic Pictet-Spengler acid-catalyzed condensation of tryptophan (2) with 3,4-dihydro-2H-pyran (3) afforded 1-(4-hydroxybutyl)-1,2,3,4-tetrahydro-b-carboline-3-carboxylic acid (4) in yields up to 60%, presumably as a mixture of diastereomers (Scheme 2). Treatment of 4 with hot acidic potassium dichromate resulted in oxidative decarboxylation to afford 1-(4-hydroxybutyl)-b-carboline (5) in yields up to 89%. Treatment of carboline alcohol 5 with hydrogen bromide followed by sodium hydroxide yielded the ring-closed zwitterionic 7, via the bromide 6. Without isolation, the crude 7 was treated with sodium borohydride to give tetracyclic amine 1 in yields of up to 40–45% overall from tryptophan. In summary, we believe that this procedure is atom-economical and practical for preparing racemic 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine (1) both efficiently and on a reasonably large scale.

中文翻译：

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色氨酸和二氢吡喃合成(±)-1,2,3,4,6,7,12,12b-八氢吲哚并[2,3-a]喹啉

Indolo[2,3-a] quinolizidine 1（方案 1）有一段有趣的历史。这种四环胺于 1950 年首先由 Keufer 合成，随后由其他几个人制备，后来才被发现是来自新几内亚树 Dracontomelum mangiferum 的天然植物生物碱。这是一种罕见的天然产物在合成后被发现的情况。几种对映选择性合成为 1 建立了 S 构型，尽管发现分离的生物碱是部分外消旋的。已经报道了其他合成。10-溴衍生物 (arborescidine A) 于 1993 年从海洋被囊动物 Pseudodistoma arborescens 中分离出来，因此，1 被命名为 desbromoarborescidine A。 尽管 1，我们觉得没有一个适合我们实验室项目所需的大规模准备。我们现在描述从色氨酸 (2) 和二氢吡喃 (3) 合成 (±)-1 的简单且原子经济的合成方法（方案 1）。经典的 Pictet-Spengler 酸催化色氨酸 (2) 与 3,4-二氢-2H-吡喃 (3) 缩合得到 1-(4-羟基丁基)-1,2,3,4-四氢-b-咔啉- 3-羧酸 (4) 的产率高达 60%，可能是非对映异构体的混合物（方案 2）。用热的酸性重铬酸钾处理 4 导致氧化脱羧，以高达 89% 的产率得到 1-(4-羟基丁基)-b-咔啉 (5)。用溴化氢和氢氧化钠处理咔啉醇 5，通过溴化物 6 产生闭环的两性离子 7。无需分离，粗品 7 用硼氢化钠处理得到四环胺 1，色氨酸的总产率高达 40-45%。总而言之，我们认为该方法对于制备外消旋 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizine (1) (1) 既高效又高效规模相当大。