| Project/Area Number |
10354010
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Organic chemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
TERUAKI Mukaiyama Tokyo University of Science, Faculty of Science, Professor, 理学部, 教授 (60016003)
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| Co-Investigator(Kenkyū-buntansha) |
ISAMU Shiina Tokyo University of Science, Faculty of Science,.Lecturer, 理学部, 講師 (40246690)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥21,400,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2001: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1998: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Taxol / Anti-tumor Agent / D-Pantolactone / Aldol Reaction / 8-Membered Ring Enone / 18-Hydroxy Taxol / 19-Hydroxy Taxol / Samarium(II)Iodide / 8員環化合物 / アルドール反応 / ヨウ化ナトリウム / 銅-亜鉛合金 / ホウ素エノラート / Knoevenagel反応 / 18-ヒドロキシタキソール / 19-ヒドロキシタキソール / 二価スズのトリフラート / 低原子価チタン / 連続的アルドール反応 / α、β-エポキシケトン / 二塩化パラジウム / ワッカー型酸化反応 / 分子内アルドール型反応 |
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| Research Abstract |
An effective method for the preparation of 8-membered ring enone, an important synthetic intermediate of anti-tumor agent Taxol, in sufficient quantities was developed. First, optically active trialkoxyaldehyde was prepared by diastereoselective dihydroxylation of the olefm derived from D-pantolactone. Secondly, 8-chloro-7-oxoaldehydes were newly synthesized by the following reactions:namely, MgBr2-OEt2-mediated diastereoselective aldol reaction of the aldehyde with ketene(trimethylsilyl) acetal, and direct chloroethylation of an ester prepared from the aldol using 1, 1-dichloroethyllithium. Then, the chiral 8-chloro-7-oxoaldehydes were converted to the 8-membered ring enone by samarium(II) iodide-mediated aldol cyclization.
Furthermore, AB ring model system of 18-hydroxy Taxol was synthesized by cesium fluoride-mediated intramolecular Knoevenagel reaction of a bicyclic precursor possessing diketoester moiety derived from 8-membered ring ketone.
A polyoxy 8-membered ring compound containing a bis-aldol skeleton, a key synthetic intermediate of 19-hydroxy Taxol, was also prepared in high yield from α, β-epoxy ketoaldehyde by the samarium(II) iodide-mediated intramolecular cyclization.
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