2006 Fiscal Year Final Research Report Summary
Synthetic Studies of Anti-tumor Natural Products Based on the Carbohydrate Transformation
| Project/Area Number |
15350027
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Organic chemistry
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
NORITAKA Chida Keio University, Faculty of Science and Technology, Professor, 理工学部, 教授 (50197612)
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| Project Period (FY) |
2003 – 2006
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| Keywords | Carbohydrate Transformation / Anti-tumor Natural Product / Taxol / Actinobolin / Fumagillol / Ferrier's Carbocyclization / Three-component Coupling Reaction / Total Synthesis |
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| Research Abstract |
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
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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
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Research Products
(12 results)
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[Journal Article] (+)-(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-o12003
Author(s)
Shigeru Ohba
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Journal Title
Acta Crystallographica Section E E59
Pages: o1476-o1477
Description
「研究成果報告書概要(和文)」より
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[Journal Article] (+)-(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-ol2003
Author(s)
Shigeru Ohba
-
Journal Title
Acta Crystallographica Section E E59
Pages: o1476-o1477
Description
「研究成果報告書概要(欧文)」より
