An Application of Electrocyclic Reaction for the Synthesis of Pyridoindole Alkaloids

电环反应在吡啶并吲哚生物碱合成中的应用

• 批准号: 11672131
• 负责人: HIBINO Satoshi
• 金额: $ 1.66万
• 依托单位: Fukuyama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672131/
• 关键词: (R)-(-)-pyridindolol K1; (R)-(-)-pyridindolol K2; (R)-(-)-pyridindolol; mecesengricin; (R)-(+)-oxopropaline D; electrocyclic reaction; synthesis; absolute congifuration; pyridindolols; oxopropaline D; mescengricin; 電子環状反応; アザヘキサトリエン系; 絶対配置

1.The first enantioselective total synthesis of (R)-(-)-pyridindolol K2 together with its enantiomer was established in a nine-step or ten step sequence based on the construction of β-carboline N-oxide through the thermal electrocyclic reaction of a 1-azahexatriene system involving the indole 2, 3-bond or the thermal cyclization of 3-ethynylindole-2-carbaldehyde oxime, followed by the Sharpless asymmetric 1, 2-dihydroxylation. In addition, the asymmetric total syntheses of (R)-(-)-pyridindolol K1 and (R)-(-)-pyridindolol were also completed using the same starting material.2.A total synthesis of α-carboline alkaloid, mescengricin has been investigated by the construction of α-carboline framework based on the thermal electrocyclic reaction of 2-azahexatriene system involving the indole 2, 3-bond. The construction of the glycerolester and the δ-lactone part at the 4-and 2-positions of α-carboline nucleus were established using 7-demethoxy-α-carboline, respectively. We are now investigation of a total synthesis of mecsengricin using 7-methoxy-α-carboline framework.3.The absolute configuration of (+)-oxopropaline D was determined as R-configuration by the asymmetric synthesis of (R)-(+)-oxopropaline D acetonide.

1.首次建立了（R）-（-）-吡啶二醇K2及其对映体的对映选择性全合成方法。该方法以1-氮杂己三烯体系中吲哚2，3-键的热电环化反应或3-乙炔基吲哚-2-甲醛肟的热环化反应为基础，经9步或10步反应得到β-咔啉N-氧化物，再经Sharpless不对称1，2-二羟基化。此外，还以相同的起始原料完成了（R）-（-）-吡啶醇K1和（R）-（-）-吡啶醇K1的不对称全合成。2.通过含吲哚2，3-键的2-氮杂己三烯体系的热电环化反应构建α-咔啉骨架，研究了α-咔啉生物碱美生菌素的全合成。用7-去甲氧基-α-咔啉分别建立了α-咔啉核4位和2位的甘油酯和δ-内酯部分的结构。3.通过不对称合成（R）-（+）-氧代丙林D丙酮化合物，确定（+）-氧代丙林D的绝对构型为R-构型。

项目成果

Naoko, Kanekiyo: "Total Syntheses of Novel Cytocidal β-Carboline Alkaloids, R-(-)-Pyridindolol K1, R-(-)-Pyridindolol K2, and Pyridindolol"J. Org. Chem.. 66(26). 8793-8798 (2001)

Naoko, Kanekiyo：“新型杀细胞β-咔啉生物碱、R-(-)-吡啶醇 K1、R-(-)-吡啶醇 K2 和吡啶醇的全合成”J. Org. 66(26)。 8798 (2001)

町支臣成: "Total Synthesis of Novel Cytocidal β-Carboline Alkaloids, oxopropalines D and G"Chem.Pharm.Bull.. 48・1. 108-113 (2000)

Masashi Machi：“新型杀细胞β-咔啉生物碱、氧代丙氨酸D和G的全合成”Chem.Pharm.Bull.. 48・1(2000)。

Tominari, Choshi: "ToTal Syntheses of Novel Cytocidal β-Carboline Alkaloids, Oxopropalines D and G"Chem. Pharm. Bull. 48(1). 108-113 (2000)

Tominari，Choshi：“新型杀细胞β-咔啉生物碱、氧代丙氨酸 D 和 G 的 ToTal 合成”，《化学公报》108-113 (2000)。

Naoko, Kanekiyo: "The Total Synthesis of R-(-)-Pyridindolol K2 and Its Enantiomeri"Heterocycles. 53(9). 1877-1880 (2000)

Naoko, Kanekiyo：“R-(-)-吡啶多洛尔 K2 及其对映异构体的全合成”杂环。

金清直子: "The First Total Synthesis of (R)-Pyridindolol K2 and Its Enantiomer"Heterocycles. 53・9. 1877-1880 (2000)

Naoko Kanekiyo：“(R)-吡啶多洛尔 K2 及其对映体的首次全合成”杂环 53・9 (2000)。