2007 Fiscal Year Final Research Report Summary
Total Synthesis of Alkaloids usingAsymmetric Catalysts
| Project/Area Number |
18590016
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Showa University |
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Principal Investigator |
ITOH Takashi Showa University, Pharmaceutical Sciences, Professor (40159885)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Kazuhiro Showa University, Pharmaceutical Sciences, Associate Professor (20208010)
KANEMITSU Takuya Showa University, Pharmaceutical Sceinces, Assistant Professor (10372913)
MIYAZAKI Michiko Showa University, Pharmaceutical Sceinces, Assistant Professor (00266165)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Organocatalvst / Asymmetric allulation / Proline Catalyst / Thiourea Catalyst / Indole Alkaloid / Isoauinoline Alkaloid |
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| Research Abstract |
We have investigated new methods for the introduction of a chiral center at C-1 position of isoquinolines and β-carbolines. In the case of isoquinolines as substrates, allylcopper reagents which have diphosphine ligands afforded moderate enantioselectivity to give 1-aIly1-1, 2, 3, 4-tetrahydroisoquinol ne derivatives. This is the fast example that the addition reaction to cyclic imines proceeded in an enantioselective manner in the presence of a chiral catalyst. The product thus obtained was used as a starting material for the enantioselective total synthesis of emetine.
The reaction system was further applied to the total synthesis of α-schulzeine, which is a natural product having a high α-glucosidase inhibitory activity. By using DTBM-segphos as a bidentate ligand, a high enantioselectivity was accomplished for the crucial asymmetric addition of allylcopper to the starting material. The allyl adduct thus obtained was transformed to the core structure of schulzeine in a stereoselectiv
… More
e manner. In addition, inhibition of a-glucosidase activity was planned to measure using bioassay.
In order to introduce an electron-deficient Cl unit at Cl position of isoquinoline derivative in an enantioselective manner, Jacobsen thiourea catalyst was applied to 3, 4-dihydroisoquinoline, and 1-cyano-1, 2, 3, 4-tetrahydroisoquinoline derivatives were abtained in a highly enantioselective manner. The product thus obtained was applied to the synthesis of several isoquinoline alkaloids such as trolline and crispine.
In the cases of 3, 4-dihydro β3-carboline derivatives, proline-catalyzed Mannich reaction proceeded to give chiral 1-substituted 1, 2, 3, 4-tetrahydro-β-carbol ne derivatives in good yields and a high enantioselectivity. In the process of the optimization of reaction conditions, it was revealed that the small amount of water in the reaction system was crucial for obtaining the high stereoselectivity. This is the fast example that the contribution of water to the stereochemistry was suggested in organocatalytic chemistry of proline. The reaction products were used as a starling material for theasymmetric total synthesis of dihydrocorynantheol and yohimbine Less
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[Presentation] Total Synthesis of Schulzeine A Using Catalytic Asymmetric Allylation of Cyclic Imines as a Key Step2007
Author(s)
K., Sugai, N., Ando, M., Miyazaki, K., Nagata, T., Itoh
Organizer
The 127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama, Japan
Year and Date
20070328-30
Description
「研究成果報告書概要(欧文)」より
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