Indole 生物鹼之合成研究

Abstract

本篇論文主要探討利用分子對稱的觀念來協助一些口引口朵生物鹼之合成研究。我們使用了Ｐｉｃｔｅｔ－Ｓｐｅｎｇｌｅｒ 反應, 以色胺與具有對稱性的醛來建立這類天然物之ｔｅｔｒａｈｙｄｒｏ－β－ｃａｒｂｏｌｉｎｅ 之架構。 (i) Ｔａｎｇｕｔｏｒｉｎｅ １ 之全合成: 經由關鍵的中間體2；化合物2具有與1 相同的立體化學。2 本身是由色胺與醛3 ─從對稱的1,3-環己二酮製備─以Ｐｉｃｔｅｔ－Ｓｐｅｎｇｌｅｒ 及 分子內Ｍｉｃｈａｅｌ 加成反應來製造。 (ii) Ｅｂｕｒｎａｍｏｎｉｎｅ 7 之全合成: 經由螺環中間體12。 (iii) Ｖａｌｌｅｓａｍｉｄｉｎｅ 20 之ｆｏｒｍａｌ 合成: 經由中間體25。 Aｓｐｉｄｏｓｐｅｒｍｉｄｉｎｅ 39 之合成研究: 經由螺環中間體47 。 (iv) Ｏｘｏｇａｍｂｉｒｔａｎｎｉｎｅ 40 之合成研究:經由中間體55。 化合物 12, 25, 47及55 的製備都使用Ｐｉｃｔｅｔ－Ｓｐｅｎｇｌｅｒ 反應由色胺及對稱的醛, 分別是11c, 24c, 49c 及 51 來製造。

Synthetic studies towards several indole alkaloids were pursued, utilizing molecular symmetry to guide the synthetic design. All tetrahydro-β-carbolines intermediates described in this dissertation were constructed by reacting tryptamine with symmetrical aldehydes via acid-induced Pictet-Spengler reaction: - Total synthesis of tangutorine 1 started from the reaction of tryptamine with aldehyde 3 - derived from symmetrical 1,3-cyclohexadione - to build the key intermediate 2 that has the correct stereochemistry of tangutorine 1. - Total synthesis of Eburnamonine 7 was conducted via a spirocyclic intermediate 12, formed by reacting tryptamine with symmetrical 5-membered ring aldehyde 11c. - Formal synthesis of vallesamidine 20 was conducted via intermediate 25, formed by reacting tryptamine with symmetrical 7-membered ring aldehyde 24. - Synthetic study on aspidospermidine 39 was conducted via a spirocyclic intermediate 47, formed by reacting tryptamine with symmetrical tetrahydropyranyl aldehyde 49c. - Synthetic study on oxogambirtannine 40 was conducted by reacting tryptamine with symmetrical 2-aryl substituted acetaldehyde 51.