| Project/Area Number |
09672287
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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 |
医薬分子機能学
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| Research Institution | Keio University |
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Principal Investigator |
KAWAMATA Takeshi School of Medicine, Keio University Assist. professor, 医学部, 講師 (80051530)
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| Co-Investigator(Kenkyū-buntansha) |
OSA Yumiko School of Pharmaceutical Sciences, Lecturer, 薬学部, 助手 (50265716)
KOBAYASHI Seiki School of Medicine, Lecturer, 医学部, 助手 (70112688)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Antimalarial activity / Santonin / Conjugated enone / alpha-cyperone / in vivo / cis-decalin derivatives / Conformational analysis / Plasmodium berghei / α,β-不飽和ケトン / α,β-エポキシケトン |
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| Research Abstract |
As our research program, various types of conjugated enone were prepared.---- i) First, the lead compound of this project, alpha-cyperone (1) reported to have a strong antimalarial activity in vitro was synthesized from santonin (2) via 3-oxo-eudesm-4-ene-12-ol (3) according to a modified literature procedure. ii) The analogues of 1 were next prepared by converting OH group of 3 into such as bromine and piperazine. III) gamma-hydroxyalkylamide derivatives (4) were prepared from 1 and 1, 2-dihydro-1 (5) by lactone cleavage with pyrrolidine, and then the corresponding unsaturated derivatives were provided by dehydration of 4 and 5 , respectively. LV) Several conjugated enone derivatives involving ketone moictey at C(1), C(2), C(3) and C(8) have been prepared starting from 1 in several steps. V) In addition, other different type of compounds involving such as epoxide group and so on were derivatized from 1. VI) Simple bicyclic enone derivatives have been synthesized from 1,3-cyclohexane dione derivatives using the well-known Robinson annelation reaction and subsequent conventional chemical modifications. VII) The derivatives thus prepared were assayed in an in vivo agaist Plasmodium berghei, and among the derivatives tested 3-oxo-eudesm-4-ene 12 Bromide (6) displayed a significant effect. while I was inactive in this experiment. VIII) Along with the above mentioned experiments aimed at the testing for the antimalarial activity of the enone derivatives derived from 2, a systematic conformatinal analysis of cis-decalin type derivatives of 2 was investigated using MM2 calculation, X-Ray crystallographic analydsis and NMR.In the course of the study an interesting findig that the ketal and thioketal of the same compound takes a different conformation was found. IX) Intoduction of OOH group into sugar derivatives was also tried.
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