Investigation and synthetic studies of bioactive Mitragyna alkaloids.

生物活性帽柱生物碱的调查和合成研究。

• 批准号: 06680553
• 负责人: TAKAYAMA Hiromitsu
• 金额: $ 1.41万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06680553/
• 关键词: Thai Traditional Medicine; Analgesic Alkaloid; Mitragyna speciosa; Chemical Constituent; Indole Alaloid; Mitragynine; Chemical Synthesis; アルカロイド合成; 化学変換反応; インドールアルカロイドの化学構造; インドールアルカロイドの合成

The leaves of Mitragyna speciosa Korth. have been known as an opium substitute in traditional use by Thai and Malay natives. Reinvestigation of the alkaloidal constituents in the leaves of the plant resulted in the isolation of a major indole alkaloid, mitragynine, and a new minor alkaloid 7alpha-hydroxy-7H-mitragynine. Starting from an optically pure alcohol, an enantioselective total synthesis of mitragynine was attained. Mitragynine was converted into the pseudoindoxyl derivative and its stereochemistry of C2, C3 was elucidated. The structure of nauclefidine, having a basic skeleton in the new type of Mitragyne alkaloids, was revised based on the total synthesis and biomimetic transformation from the vincoside lactam. The crude alkaloid mixture and mitragynine showed non-narcotic antinociceptive activities and inhibited contraction of smooth muscle.

紫穗槐的叶子。在泰国和马来当地人的传统使用中，被认为是鸦片的替代品。重新调查的植物叶中的生物碱成分导致分离的主要吲哚生物碱，mitragynine，和一个新的次要生物碱7 α-羟基-7H-mitragynine。以光学纯醇为起始原料，实现了对映选择性全合成。将Mitragynine转化为假吲哚酚衍生物，并阐明了其C2，C3的立体化学。基于长春苷内酰胺的全合成和仿生转化，修正了新类型的Mitragyne生物碱中具有基本骨架的nauclefidine的结构。结果表明，混合生物碱和mitragynine具有非麻醉性的镇痛作用，并能抑制平滑肌的收缩。

项目成果

Dhavadee Ponglux: "A new indole alkaloid,Tα-hydroxy-TH-mitragynine,from Mitragyna speciosa n Thailand" Planta Medica. 60. 580-581 (1994)

Dhavadee Ponglux：“一种新的吲哚生物碱，Tα-羟基-TH-帽柱木碱，来自泰国的帽柱木”Planta Medica。 60. 580-581 (1994)

Kinzo Matsumoto: "Suppressive effect of Mitragynine on 5-methoxy-N,N-dimethyltryptamine-induced Head Twitch Response in Mice." Pharmacol.Biochem.Behav.in press.

Kinzo Matsumoto：“帽柱木碱对 5-甲氧基-N,N-二甲基色胺诱导的小鼠头部抽搐反应的抑制作用。”

Hiromitsu Takayama: "On the indole alkaloid, nauclefidine ; Structure revision, synthesis, and biomimetic transformation from the vincoside lactam." Tetrahedron Lett.35. 8813-8816 (1994)

Hiromitsu Takayama：“关于吲哚生物碱、nauclefidine；长春苷内酰胺的结构修正、合成和仿生转化。”

Hiromitsu Takayama: "The first total synthesis of (-) -mitragynine, an analgesic indole alkaloid in Mitragyna speciosa." Tetrahedron Lett.36. 9337-9340 (1995)

Hiromitsu Takayama：“首次全合成 (-)-帽柱木碱，这是帽柱木中的一种镇痛吲哚生物碱。”

Kinzo Watanabe: "Suppressive effect of Mitragynine on 5-methoxy-N,N-dimethyl-tryptamine-induced head twich response in mice." Pharmacol. Biochem, Behav.(in press).

Kinzo Watanabe：“帽柱木碱对 5-甲氧基-N,N-二甲基-色胺诱导的小鼠头部抽搐反应的抑制作用。”