| Project/Area Number |
13470473
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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 | Tokyo University of Science |
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Principal Investigator |
KOBAYASHI Susumu Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70101102)
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| Co-Investigator(Kenkyū-buntansha) |
HOSOKAWA Seijiro Waseda University, School of Science and Engineering, Lecturer, 理工学部, 講師 (10307712)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | Norzoanthamine / Epolactaene / Akaterpin / Biologically Active Natural Product / Total Synthesis / Vinylogous Mukaiyama Aldol / インターロイキン-6 / アポトーシス誘導作用 / PI-PLC |
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| Research Abstract |
Norzoanthamine : Treatment of appropriately functionalized precursor was treated with AcOH-H_2O resulted in the tandem cyclization to obtain the bisaminal structure (CDEFG ring moiety), a most characteristic segment of norzoanthamine. Synthetic investigation toward a total synthesis of norzoanthamine was also attempted. Starting from Wieland-Miescher ketone or Hajos-Parrish ketone, we were able to construct a ABC ring moiety of norzoanthamine. We are currently trying to prepare a cyclization precursor for completion of the total synthesis.
Epolactaene : We have already completed the total synthesis of epolactaene by developing a novel method, that is a fluoride anion-catalyzed aldol type reaction of trimethylsilylated α, β-epoxy-γ-lactone with aldehyde. The drawback of this methodology is that osidation of the secondary hydroxyl group is necessary for the synthesis of epolactane. We then examined an alternative and efficient approach to solve this problem. Finally, we were able to develop a single step procedure by the reaction of trimethylsilylated α, β-epoxy-γ-lactone with acid fluoride in the presence of a catalytic amount of fluoride anion. Epolactane was found to enhance an apoptosis of a cancer cell line (BALL-1 cell) in addition to an inhibitory effect on a cell proliferation. These results are quite interesting from a biological point of view, and we were particularly interested in an identification of an intracellular protein target of epolactaene. In order to do this, molecular probe of epolactaene was prepared.
Akaterpin : We have previously shown that the relative stereochemistry of the upper decalin of akaterpin is a cis-fused decalin. In order to construct a bis decalin structure, we attempted an intermolecular Diels-Alder reaction of enone with upper decalin and vinyl cyclohexene. The reaction was found to proceed in a stereoselective manner (9 : 1), and the major isomer was found to have a natural stereochemistry by correlating to akaterpin.
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