Chemical Study of Alkaloids in Tropical Medicinal Plants as the Lead-Compounds to Develop New Biologically Functional Molecules.

热带药用植物中生物碱作为先导化合物的化学研究，以开发新的生物功能分子。

• 批准号: 08680627
• 负责人: TAKAYAMA Hiromitsu
• 金额: $ 1.6万
• 依托单位: Chiba 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-08680627/
• 关键词: Medicinal plant; Mitragyna speciosa; Hunteria zeylanica; Nauclea orientalis; Indole alkaloid; Isolation and structure elucidation; Chemical synthesis; Opioid agonist; Mitragynine; 鎮痛活性; Nauclea orientalis

1.The leaves of Mitragyna speciosa Korth.have been known as an opium substitute in troditional use by Thai and Malay natives. Reinvestigation of the alkaloidal constituents of the plant in Malaysia resulted in the isolation of four new indole alkaloids, whose unusual structures were elucidated by total synthesis and/or spectroscopic analysis. New synthtic strategy for the chiral total syntheses of minor Mitragyna alkaloids was studied. A potent opioid agonistic property of mitragynine and mitragynine pseudoindoxyl was clarified in vitro experiments. Mitragynine pseudoindoxyl, whose agonistic potency is 20-50 fold greater than that of morphine, acts on mu-and delta-opioid receptors.2.To establish the synthetic route of new Sarpagine-type Hunteria alkaloids, a model experiment was done, through which a monoterpenoid indole alkaloid, geissoschizine, was synthesized via radical cyclization strategy. Inhibitory effects of corymine, an alkaloidal component from Hunteria zeylanica, on glycine receptors was found.3.From Nauclea orientalis in Thailand, seven non-alkaloidal and two glycosidic indole compounds were isolated. 10-Hydroxystrictosamide and its pentaacetyl derivative were prepared to examne the C3 stereochemistry.

1.泰国和马来土著人在热带地区使用Mitragyna speciosa Korth.的叶子作为鸦片替代品。重新调查的生物碱成分的植物在马来西亚导致四个新的吲哚生物碱的分离，其不寻常的结构被阐明的全合成和/或光谱分析。本文研究了手性全合成少数几种Mitragyna生物碱的新的手性策略。一个有效的阿片激动特性的mitragynine和mitragynine pseudoindoxyl澄清在体外实验。Mitragynine pseudoindoxyl作用于μ-和δ-阿片受体，其激动效力是吗啡的20-50倍。2.为了建立新的Sarpagine型Hunteria生物碱的合成路线，进行了模型实验，通过自由基环化策略合成了单萜吲哚生物碱Geissocelline。3.从泰国乌檀中分离得到7个吲哚类化合物和2个吲哚类化合物。10-合成了羟基异柳胺及其五乙酰基衍生物，考察了其C3立体化学。

项目成果

K.Matsumoto: "Suppressive Effect of Mitragynine on the 5-Methoxy-N,N-dimethyltryptamine-Induced Head-Twitch Response in Mice" Pharmaco.Biochem.Behav.57・1. 319-323 (1997)

K.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”Pharmaco.Biochem.Behav.57・1 (1997)。

H.Takayama, et al.: "Biomimetic Synthesis of Nauclea Indole Alkaloids, Naucleidinal and 3-epi-Naucleidinal, by Stereoselective Rearrangement of Strictosamide and the Vincoside Lactam Aglycons." Chem.Pharm.Bull.44. 2192-2194 (1996)

H.Takayama 等人：“通过立体选择性重排单糖酰胺和长春糖苷内酰胺苷元仿生合成 Nauclea 吲哚生物碱、Naucleidinal 和 3-epi-Naucleidinal”。

H.Takayama: "Hunterioside B,A Disaccharide Carrying Monoterpenoid Indole Alkaloid,from Hunteria zeylanica." Heterocycles. 47・1. 87-90 (1998)

H.Takayama：“Hunterioside B，一种携带单萜吲哚生物碱的二糖，来自Hunteria zeylanica 47·1（1998）。”

H.Takayama: "Stereochemical Assignment of Pseudoindoxyl Alkaloids" Heterocycle. 42・1. 87-92 (1996)

H. Takayama：“拟吲哚酚生物碱的立体化学分配”杂环42・1（1996）。

H.Takayam, et al.: "Hunterioside B,A Disaccharide Carrying Monoterpenoid Indole Alkaloid, from Hunteria zeylanica." Heterocycles. 47. 87-90 (1998)

H.Takayam 等人：“Hunterioside B，一种携带单萜吲哚生物碱的二糖，来自Hunteria zeylanica。”