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Synthetic Studies of Anti-tumor Natural Products Based on the Carbohydrate Transformation

基于碳水化合物转化的抗肿瘤天然产物的合成研究

基本信息

批准号：
15350027
负责人：
NORITAKA Chida
金额：
$ 7.3万
依托单位：
KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

The development of efficient chemical process for the synthesis of biologically active natural product is highly important task in modern synthetic organic chemistry. In this study, synthesis of natural products possessing significant anti-tumor activities, such as taxol, actinobolin and fumagillol based on the carbohydrate transformation was investigated. Carbohydrates have been produced by plants in huge quantities without causing any negative effect to the environment of the earth and thus are considered to be important carbon resources.In the project of taxol synthesis, D-glucal which is one of the most readily available carbohydrates, was converted into the highly functionalized cyclohexenone derivative utilizing Ferrier's carbocyclization reaction as the key step. Three-component coupling reaction of the cyclohexenone with vinyl metal species and formaldehyde effectively afforded the C-ring of taxol.Coupling reaction of the C-ring with A-ring, followed by further manipulation gav … More e the cyclohexenone derivative possessing an aldehyde function. SmI2 mediated reductive cyclization successfully afforded the taxane skeleton in good yield. Introduction of the carbon-carbon double bond, which would complete the total synthesis, is now under investigation.In the synthetic study of actinobolin, total synthesis of both enantiomers of the target compound was successfully achieved.Three-component coupling reaction of the cyclohexenone derived from D-glucose with vinyl metal species and hydroxyaldehyde was employed as the key transformation. It was found that the stereochemical control of the aldol reaction process was possible by the choice of the protecting group of the hydroxyaldehyde and the solvents.In fumagillol synthesis, Claisen rearrangement of the cyclohexenol derived from D-glucose effectively generated the carbon-carbon bond stereoselectively. Further transformation of the rearranged product provided the Sorensen's intermediate for fumagillol, completing the formal total synthesis. Optimization of the reaction conditions is currently under way. Less

开发高效的化学方法合成具有生物活性的天然产物是现代有机合成化学的重要任务。本论文主要研究了基于糖基转化的紫杉醇、放线菌素和烟曲霉醇等具有显著抗肿瘤活性的天然产物的合成。碳水化合物是一种重要的碳源，是植物产生的大量碳水化合物，对地球环境无任何负面影响，在紫杉醇合成项目中，利用Ferrier碳环化反应将D-葡萄糖醛转化为高度功能化的环己烯酮衍生物。环己烯酮与乙烯基金属物种和甲醛的三组分偶联反应有效地得到了紫杉醇的C-环，C-环与A-环的偶联反应，然后进一步操作，得到了紫杉醇的C-环。 ...更多信息即具有醛官能团的环己烯酮衍生物。SmI 2介导的还原环化反应成功地以高产率得到了紫杉烷骨架。在放线菌素的合成研究中，以D-葡萄糖为起始原料，通过环己烯酮与乙烯基金属物种和羟基醛的三组分偶联反应，成功地实现了目标化合物两个对映体的全合成。研究发现，通过选择羟基醛的保护基和溶剂，可以对羟醛缩合反应进行立体化学控制，在烟曲霉醇的合成中，D-葡萄糖衍生的环己烯醇的Claisen重排有效地立体选择性地生成了碳-碳键。重排产物的进一步转化提供了烟曲霉醇的索伦森中间体，完成了正式的全合成。目前正在优化反应条件。少

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

(+)-(1S,2S,4S,4aR,5R,6S,9S,10S)-4-Benzyloxy-9,10-(carbonyldioxy)-1-methoxymethoxy-4a,6,8,8-tetramethyl-7-methyl enedodecahydro-6,9-ethanobenzocyclooctene-5-o1

( )-(1S,2S,4S,4aR,5R,6S,9S,10S)-4-苄氧基-9,10-(羰二氧基)-1-甲氧基甲氧基-4a,6,8,8-四甲基-7-甲基

DOI：
发表时间：
2003
期刊：
Acta Crystallographica Section E E59
影响因子：
0
作者：
Satoshi Imuta;Takafumi Kitawaki;Hiroyuki Ohno;Satoshi Imuta;Takafumi Kitawaki;Hiroyuki Ohno;Kazuo Kurosawa;Satoshi Imuta;Takafumi Kitawaki;Hideyuki Sato;Takafumi Kitawaki;Kazuo Kurosawa;Masahiro Bohno;Masahiro Bohno;Masahiro Bohno;佐藤英之;Satoshi Imuta;Shigeru Ohba
通讯作者：
Shigeru Ohba

New synthesis of (−)- and (+)-actinobolin from d-glucose

DOI：
10.1016/s0040-4039(03)01186-9
发表时间：
2003-06
期刊：
Tetrahedron Letters
影响因子：
1.8
作者：
Satoshi Imuta;S. Ochiai;Miho Kuribayashi;N. Chida
通讯作者：
Satoshi Imuta;S. Ochiai;Miho Kuribayashi;N. Chida

One-step construction of carbazoles by way of the palladium-catalyzed double N-arylation reaction and its application to the total synthesis of murrastifoline-A

DOI：
10.1016/j.tet.2006.04.087
发表时间：
2006-07-17
期刊：
TETRAHEDRON
影响因子：
2.1
作者：
Kitawaki, Takafumi;Hayashi, Yoko;Chida, Noritaka
通讯作者：
Chida, Noritaka

(+)-(1S,2S,4S,4aR,5R,6S,9S,10S)-4-Benzyloxy-9,10-(carbonyldioxy) 1-methoxymethoxy-4a,6,8,8-tetramethy1-7-methylenedodecahydro- 6,9-ethanobenzocyclooctene-5-ol

( )-(1S,2S,4S,4aR,5R,6S,9S,10S)-4-苄氧基-9,10-(羰二氧基) 1-甲氧基甲氧基-4a,6,8,8-四甲基1-7-亚甲基十氢-

DOI：
发表时间：
2003
期刊：
Acta Crystallographica Section E E59
影响因子：
0
作者：
Satoshi Imuta;Takafumi Kitawaki;Hiroyuki Ohno;Satoshi Imuta;Takafumi Kitawaki;Hiroyuki Ohno;Kazuo Kurosawa;Satoshi Imuta;Takafumi Kitawaki;Hideyuki Sato;Takafumi Kitawaki;Kazuo Kurosawa;Masahiro Bohno;Masahiro Bohno;Masahiro Bohno;佐藤英之;Satoshi Imuta;Shigeru Ohba;Satoshi Imuta;Shigeru Ohba
通讯作者：
Shigeru Ohba

Total Synthesis and Biological Activities of (+)‐Sulfamisterin (AB5366) and Its Analogues.

(+)-磺胺嘧啶 (AB5366) 及其类似物的全合成和生物活性。