1999 Fiscal Year Final Research Report Summary
Syntheses of Alkaloids Using Palladium-Catalyzed Asymmetric Synthesis
| Project/Area Number |
09470478
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MORI Miwako Hokkaido Univ., Grad. School of Pharm. Sci., Professor, 大学院・薬学研究科, 教授 (80001981)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Yoshihiro Hokkaido Univ., Grad. School of Pharm. Sci., Lecturer, 大学院・薬学研究科, 講師 (90226019)
NISHIDA Mayumi Hokkaido Univ., Grad. School of Pharm. Sci., Associate Professor, 大学院・薬学研究科, 助教授 (70130044)
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| Project Period (FY) |
1997 – 1999
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| Keywords | palladium complex / π-allyl palladium complex / asymmetric synthesis / pretazetine / crinamine / kinetic resolution / haemanthidine / carbonyl-ene reaction |
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| Research Abstract |
Palladium-catalyzed asymmetric synthesis of methyl 2-arylcyciohexenyl carbonate was realized using (S)-BINAPO as a chiral ligand. Using this method, we succeeded in the total syntheses of (-)-mesembrane and (-)-mesembrine by combination of palladium-catalyzed amidation followed by zirconium-promoted cyclization. The Amaryllidaceae alkaloids have been of interest as synthetic targets due to their wide range of biological activities. Over 100 alkaloids have been isolated from memberes of the Amaryllidaceae, and most of these may be classified into eight skeletally homogeneous subgroups. We accomplished the first asymmetric total syntheses of the crinane-type alkaloids, (+)-crinamine, (-)-haemanthidine, and (+)-pretazettine. The starting cyclohexenyl amine was obtained by palladium-catalyzed asymmetric amination in 80% yield and with 74% ee. The product was recrystalyzed from MeOH. Interestingly, (-)-cyclohexenyl amine derivative with 99% ee was obtained from the mother liquor. Intramolecular carbonyl-ene reaction proceeds in a highly stereoselective manner to give hexahydroindole derivative as the sole product. In the Lewis acid-catalyzed carbonyl-ene reaction, an interesting rearrangement product was isolated in high yield. From this product, the above alkaloids, (+)-crinamine, (-)-haemanthidine, and (+)-pretazettine, were synthesized in very few steps. The structure of intermediary palladium complex was confirmed by X-ray crystallography.
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