Development of useful sequential cyclization of acrylate derivatives and applications to bioactive natural products synthesis
| Project/Area Number |
15590027
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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 | Meiji Pharmaceutical University |
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Principal Investigator |
NAGAOKA Hiroto Meiji Pharmaceutical University, The Pharmaceutical Department, Professor, 薬学部, 教授 (30155915)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | samarium(II) iodide / cyclization / ring-expansion / bicyclo[4.3.0]nonan-8-ones / bicyclo[3.3.0]octan-3-ones / hirustene / eleman-8b.12-olide / gibberellin A_1 / 環拡大 / アクリル酸エステル / 全合成 / ジベレリンA_1 / ピシクロ[3.3.0]オクタノン / 1-desoxyhypnophilin |
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| Research Abstract |
Numerous efforts have been made to produce bicyclic cyclopentanones, not only in consideration of their abundance in nature, but also their usefulness as versatile synthetic building blocks. The tandem reductive coupling-Dieckmann condensation reaction has been found quite useful as a one-step process for effectively producing oxacyclopentanecarboxylates from acrylate derivatives (α,β-unsaturated esters). Electrohydrodimerization and metal-induced cyclization of cinnamate derivatives are methods generally applied for this purpose but to none has been shown to produce in an intramolecular manner bicyclic oxacyclopentanecarboxylate. The authors established an effective and direct one-step process for obtaining bicyclo[4.3.0]nonan-8-ones and bicyclo[3.3.0]octan-3-ones from simple bis-α,β-unsaturated esters using one electron transfer reagent SmI_2 in the presence of methanol in trace amount. Severely strained bicyclo[3.3.0]octane warped trans ring system and tricyclic keto esters were also synthesized by the reaction, but the formation of bicyclo[5.3.0]decan-9-ones and bicyclo[6.3.0]undecan-10-ones failed to occur. For the preparation of these system, the novel ring-expansion reaction of 1,2-cyclobutanedicarboxylates, readily accessible from the corresponding cycloalkenes or acrylate derivatives, via Sm(II)-induced sequential reductive fragmentation-Dieckmann condensation was developed. This reaction is the first instance of the transformation of cyclobutanes to cyclopentanes via tandem reductive fragmentation-Dieckmann condensation. Forthermore, the formal total syntheses of triquinane-type sesquiterpines, hirustene, and eleman-type sesquiterpenoid, eleman-8β,12-olide, and the total synthesis of gibberellin A_1 were conducted with Sm(II) iodide-induced cyclization of acrylate derivatives as key steps.
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Report
(3 results)
Research Products
(8 results)
