2007 Fiscal Year Final Research Report Summary
Development of carbon-carbon bond forming reaction under environmentally benign conditions and its application to combinatorial synthesis
| Project/Area Number |
16390010
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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 | Kobe Pharmaceutical University |
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Principal Investigator |
NAITO Takeaki Kobe Pharmaceutical University, 薬学部, Professor (00068339)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Okiko Kobe Pharmaceutical University, 薬学部, Professor (90102110)
UEDA Masafumi Kobe Pharmaceutical University, 薬学部, Assistant Professor (00340935)
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| Project Period (FY) |
2004 – 2007
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| Keywords | environmentally benign / radical reaction / carbon-carbon bond formation / one-pot / aqueous solvent / rearrangement / rearrangement / domino reaction |
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| Research Abstract |
1. Carbon-carbon bond formation by radical reaction
The use of water as a solvent has generated considerable interest from both economical and environmental points of view. We have developed novel carbon-carbon forming reactions employing radical as a crucial reaction species and aqueous media as solvent. Newly-found radical reactions are proved to be synthetically useful by completing synthesis of several biologically active compounds.
We firstly investigated selective and efficient alkyl radical addition to various types of imine derivatives. Structure of an intermediate generated by alkyl radical addition to oxime ethers was firmly established by carbon, hydrogen, and boron NMR analyses. Total synthesis of an abnormal amino acid, penmacric acid was completed for the first time via our radical addition reaction. Domino type of radical addition-cydization-(trapping) reaction was also developed and used for efficient construction of functionalized cyclic compounds. Novel synthetic route for Martinellic acid, isolated as a first pyrroloquinoline alkaloid was developed.
Newly-found radical addition-aldol type of reaction is expected to be an efficient and environmentally benign reaction.
2. Rearrangement reaction under mild conditions
Rearrangement reaction is one of atom-economy reactions. During our systematic investigation on 1,2-Wittig rearrangement of hydroximates, we completed the total synthesis of (+)-cytoxazone. In our continuing study on [3, 3]-sigmatropic rearrangement of hydrazones under the acylating conditions, we developed a short step and efficient method for the synthesis of benzofurans via acylation of O-aryl oxime ethers under very mild reaction conditions, even in the presence of free hydroxyl group.
As an environmentally benign synthetic method, one-pot synthesis of N-alkyl arylamines from oxime ethers was also developed.
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