Synthesis of Optically Active Lysergic Acid

光学活性麦角酸的合成

• 批准号: 08672452
• 负责人: YOKOYAMA Yuusaku
• 金额: $ 0.32万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672452/
• 关键词: biosynthesis; ergot alkaloids; tryptophan; Heck reaction; optically active; palladium catalyzed cyclization; DMAT; chanoclavine-I; 閉環反応; 光学活性

1.Total synthesis of optically acitive chanoclavine-I was successfully accomplished starting from optically active N_<alpha>-tert-butoxycarbony1-4-bromotryptophan methyl ester (1). The key step was the palladium catalyzed cyclization (Heck reaction) of alpha, beta-conjugate ester(2)which was obtained by the conversion of alpha-carboxyl group to aldehyde followed by Wittig reaction, to form tricyclic chclohexa [c, d] indole skeleton (ergoline skeleton).2.Total synthesis of Y,Y-dimethylallyltryptophan (DMAT,3), which was the common intermediate of all ergot alkaloids biosynthesis, was accomplished starting from 1. The key step was Heck reaction of 1 with 1,1-dimethylallylalcohol (4) to form of N_<alpha>-tert-butoxycarbonyl-4- (2-hydroxy-2-methyl-1-butene-1-yl) -1-tosyltryptophan (5). Compound (5) was dehydrated with TsOH/benzene to form dine (6) which was converted to olefin (7) by 1,4-reduction with Mg/MeOH.3.Decarboxylative cyclization 5 was failed under various conditions (radical or photo reactions of its thiol, selenol or oxime esters).

1.以光学活性的N-<alpha>叔丁氧羰基-4-溴色氨酸甲酯（1）为起始原料，成功地全合成了光学活性的裸花黄素-I。关键步骤是钯催化的环合反应α，β-共轭酯（2）通过α-羧基转化为醛，然后进行Wittig反应而得到，通过Heck反应形成三环氯己[c，d]吲哚骨架2.麦角生物碱生物合成的共同中间体Y，Y-二甲基烯丙基色氨酸（DMAT，3）的全合成，是从1开始的。关键步骤是1与1，1-二甲基烯丙醇（4）发生Heck反应生成N-<alpha>叔丁氧羰基-4-（2-羟基-2-甲基-1-丁烯-1-基）-1-对甲苯磺酰基色氨酸（5）。化合物（5）经TsOH/苯脱水生成二氢呋喃（6），再经Mg/MeOH 1，4-还原生成烯烃（7）。

项目成果

Kazuhiro Kondo: "The ortho-Substituted N,N-Diacetylaniline as a Selective Acetylating Reagent" Tetrahdron Lett.,. 38・21. 3751-3754 (1997)

Kazuhiro Kondo：“作为选择性乙酰化试剂的邻位取代的 N,N-二乙酰苯胺”Tetrahdron Lett., 3751-3754 (1997)。

Yuusaku Yokoyama: "A New Route for the Tricyclic Indole System:A Useful Intermediate for Ergot Alkaloids" Heterocycles,. 46. 57-60 (1997)

Yuusaku Yokoyama：“三环吲哚系统的新路线：麦角生物碱的有用中间体”杂环，。

Hideharu Suzuki: "A.General Synthetic Route for 1-Substituted 4-Oxygenated β-Carbolines" Tetrahedron. 53・5. 1593-1606 (1997)

Hideharu Suzuki：“1-取代的 4-氧化 β-咔啉的一般合成路线”四面体 53・5 (1997)。

Yuusaku Yokoyama: "Total Synthesis of Optically Active Chanoclavine-I" Tetrahedron Lett.37. 9309-9312 (1996)

Yuusaku Yokoyama：“光学活性 Chanoclavine-I 的全合成”四面体 Lett.37。

Yasuoki Murakami: "Fischer Indolization of 2-Sulfonyloxyphenyldrazones : A New and Practical Approach for Preparing 7-Oxygenated Indoles" Tetrahedron. 54・1. 45-64 (1998)

Yasuoki Murakami：“2-磺酰氧基苯基德拉酮的费舍尔吲哚化：制备 7-含氧吲哚的新实用方法”Tetrahedron 54・1（1998）。