Chemical Study on Camptothecinoid Glycosidic Alkaloids of Ophiorrhiza pumila

蛇根喜树碱苷类生物碱的化学研究

• 批准号: 02670942
• 负责人: AIMI Norio
• 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 General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670942/
• 关键词: Ophiorrhiza pumila; chaboside; Rubiaceae; alkaloid; camptothecins; glycoside; total synthesis; structure determination; Ophiorrhiza pumila; 全合成; 抗腫瘍活性天然物

A Rubiaceous plant, ophiorrhiza pumila distributes in the Amami and Ryukyu islands, a southern region of Japan under subtropical climate. The foregoing studies revealed that this species has special potency as a resource plant of important lead compounds towards developing clinical drugs. Until 1990 we succeeded in isolating pumiloside and deoxypumiloside, new type of camptothecinoid glucosides. They were f ound to be the longsought biosynthetic intermediates of camptothecin group of quinoline alkaloids. Further study allowed us to isolate another member of glucocamptothecinoid, a compound named chaboside. The present project deals with the structure elucidation' and total synthesis of this compound.Chaboside, C_<28>H_<32>O_<10>, was shown to be the first natural glucosidic campto hecin. The A ring was foun carry one methoxyl and one glucosyl oxy groups. ^1H-and ^<13>C-NMR spectra indicated the positions of the substituents ; C-9 for methoxyland C-10 for glucosyloxy groups.Then synthetic study on chaboside and related alkaloids were undertaken. A general synthetic strategy developed by Shanghai group was employed. The Aring segment with glucoside moiety at the proper position was prepared from o-vanillin. This compound was condensed with chiral CDE ring moiety prepared by the method of the research group of Daiichi Pharmaceutical Co. The synthesized material was shown to be completely identical with the natural chaboside. Here the structure of chaboside including the absolute configuration at C-20 was proved. Similarly chaboside aglycone, i. g. 9-methoxy-10-hydroxycamptothecin, and a new natural product, 10-hydroxy-20-deoxycamptothecin, were synthesized.

矮蛇根草是蔷薇科植物，分布于日本南部的奄美群岛和琉球群岛，属亚热带气候。上述研究表明，该种植物作为重要先导化合物的资源植物，对开发临床药物具有特殊的潜力。直到1990年，我们才成功地分离到新的喜树碱甙类化合物--pumiloside和deoxypumiloside。它们是人们长期寻找的喹啉类生物碱喜树碱类的生物合成中间体。进一步的研究使我们能够分离出葡萄糖喜树碱的另一个成员，一种名为chaboside的化合物。本课题对该化合物进行了结构鉴定和全合成，并<28><32><10>首次发现了天然葡萄糖苷类化合物campto hecin，C_ H_ O_。发现A环上带有一个甲氧基和一个葡萄糖基氧基。~ 1H-NMR和~ 1C-NMR<13>谱确定了取代基的位置，C-9为甲氧基，C-10为葡萄糖氧基。采用上海组提出的通用综合策略。以邻香草醛为原料，制备了在适当位置带有葡萄糖苷部分的Aring片段。该化合物与第一制药公司研究组制备的手性CDE环部分缩合，合成的物质与天然chaboside完全相同。在此证明了chaboside的结构，包括C-20的绝对构型。类似地，chaboside苷元，i. G.合成了9-甲氧基-10-羟基喜树碱和新天然产物10-羟基-20-脱氧喜树碱。

项目成果

N.Aimi,H.Hoshino,M.Nishimura,S.Sakai J.Haginiwa: "Chaboside,First Natural Glycocamptothecin found from Ophiorrhiza pumila" Tetrahedron Letters. 36. 5169-5172 (1990)

N.Aimi、H.Hoshino、M.Nishimura、S.Sakai J.Haginiwa：“Chaboside，从蛇根草中发现的第一个天然糖喜树碱”四面体字母。

N. Aimi, H. Hoshino, M. Nishimura, S. Sakai, J. Haginiwa: "Chaboside, First Natural Glycocamptothecin found from Ophiorrhiza pumila" Tetrahedron Letters. 36. 5169-5172 (1990)

N. Aimi、H. Hoshino、M. Nishimura、S. Sakai、J. Haginiwa：“Chaboside，从蛇根草中发现的第一个天然糖喜树碱”四面体快报。

N.Aimi,H.Hoshino,M.Nishimura,S.Sakai,J.Haginiwa: "Chaboside,First Natural Glycocamptothecin found from Ophiorrhiza pumila" Tetrahedron Letters. 36. 5169-5172 (1990)

N.Aimi、H.Hoshino、M.Nishimura、S.Sakai、J.Haginiwa：“Chaboside，从蛇根草中发现的第一个天然糖喜树碱”四面体字母。

N.Aimi,H.Hoshino,M.Nishimura,S.Sakai,J.Haginiwa: "Chaboside,first natural glycocampthotecin found from ophiorrhiza pumila" Tetrahedron Letters. 36. 5169-5172 (1990)

N.Aimi、H.Hoshino、M.Nishimura、S.Sakai、J.Haginiwa：“Chaboside，从蛇根中发现的第一个天然糖喜树碱”四面体字母。