1994 Fiscal Year Final Research Report Summary
Synthetic studies on Antitumor Antibiotic and Biological Activity
| Project/Area Number |
05671865
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
医薬分子機能学
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| Research Institution | Chiba University |
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Principal Investigator |
NAKAGAWA Masako Chiba University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40009171)
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| Co-Investigator(Kenkyū-buntansha) |
KAWATE Tomohiko Chiba University, Faculty of Pharmaceutical Sciences, research associate, 薬学部, 助手 (50195111)
TORISAWA Yasuhiro Chiba University, Faculty of Pharmaceutical Sciences, research associate, 薬学部, 講師 (80119601)
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| Project Period (FY) |
1993 – 1994
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| Keywords | manzamine A / Diels-Alder Reaction / manzamine C / dynamicin A / Danishefsky's diene / 3-alkyldihydropyridinone / cytotoxicity / azocine |
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| Research Abstract |
I.Approaches to the total synthesis of manzamineA
1. For the challenging construction of the complex hydroisoquinoline framework of manzamine A,we have been investigating a feasibility of the Diels-Alder reaction of suitably protected 3-alkyldihydropyridinones. Through an efficient intrmolecular D-A reaction of the dihydropyridinone and Danishefsky's diene, we have successfully constructed the central tetracyclic core of manzamine A.
For the attainment of the more convergent synthetic route, it is preferable use the azocine-containing dienophile. For the preparation of this new dienophile as an optically active form, we investigated the two new synthetic route starting from L-serine derivative.
2. According to the computer assisted conformational analysis of manzamine A and C,we have succeeded the synthesis of the natural manzamine C,its trans-isomer, and ring-modified analogs. All of the manzamine C analogs its trans-isomer showed similar in vitro cytotoxic activity to manzamine C itself.
II.Approaches to the total synthesis of dynamicine A
The phenanthridine key intermediate for the total synthesis of dynamicin A,a potent antitumor antibiotic, has been synthesized by our synthetic methodology used for manzamine A synthesis.
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