1997 Fiscal Year Final Research Report Summary
Synthetic Studies on Nitrogen Containing Natural Products
| Project/Area Number |
08457582
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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 |
Chemical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUKUYAMA Tohru The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (10272486)
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| Project Period (FY) |
1996 – 1997
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| Keywords | indole Synthesis / Tabersonine / Vincadifformine / protective group / sulfonamides / diamines / Gelsemine / Diels-Alder reaction |
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| Research Abstract |
In connection with our recent report on the novel use of 2- and 4-nitrobenzenesulfonamide that provides an efficient way for the synthesis of secondary amines, we have developed 2,4-dinitrobenzenesulfonamides amine protective group, which undergo exceptionally facile and selective deprotection in the presence of 2-nitrobenzenzenesulfonamides. Combination of these sulfonamides could be used for the preparation of wide variety of diamines.
Using our protocol for the preparation of secondary amines and indole synthesis previously reported, we could achieve highly efficient total syntheses of ((]SY.+-。[))-vincadifformine and (-) -tabersonine. The common 3-indole ethanol part for both total syntheses was prepared from isonitrile, followed by introduction of acrylate moiety on the indole 2-position in one pot. Condensation of the indole part and the amine moiety protected as 2,4-dinitrobenzenesulfonamide under Mitsunobu condition gave cyclization precursors. Removal of Boc protective groups on indole NH and 2,4-dinitrosulfonamide group in mild condition furnished the desired pentacyclic skeletons via dihydrosecodine intermediate. These syntheses represents the most straightforward way to synthesize this class of compounds.
Controlling the stereochemistry of the spino-oxiindole moiety remained as a problem in the reported total syntheses of gelsemine by three groups. We could overcome this issue by the introduction of iodine substituent on the oxiindole unit and could achieve stereocontrolled total synthesis of gelsemine in racemic form. Furthermore, the key intermediate in our racemic total synthesis was synthesized as an optically active compound by asymmetric Diels-Alder reaction and Lewis acid mediated rearrangement of epoxybicyclo [2.2.1] heptene system as key reactions.
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