2004 Fiscal Year Final Research Report Summary
Chemical Synthesis of marine pyrrole alkaloids effective against multidrug-resistant cancers
| Project/Area Number |
14580612
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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 |
Bioorganic chemistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
IWAO Masatomo Nagasaki University, Engineering, Professor, 工学部, 教授 (00100892)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUDA Tsutomu Nagasaki University, Engineering, Research associate, 工学部, 助手 (80295097)
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| Project Period (FY) |
2002 – 2004
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| Keywords | multidrug-resistant cancer / marine pyrrole alkaloids / lamellarin G trimethyl ether / lamellarin D / lamellarin L / lamellarin N / permethyl storniamide A / ningalin B |
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| Research Abstract |
We have developed an efficient procedure for the synthesis of 3,4-diarylpyrrole-type marine alkaloids, which exhibit cytotoxic activity against multidrug-resistant(MDR) cancer cells.
Hinsberg-type condensation of N-alkyliminodiacetates with dimethyl oxalate produced N-alkyl-3,4-dihydroxypyrrole-2,5-dicarboxylates. The bistriflate derivatives of the 3,4-dihydroxypyrroles were cross-coupled with a wide range of arylboronic acids in the presence of Pd(0) catalysts to give the 3,4-diarylpyrrole-2,5-dicarboxylates in excellent yields. The stepwise introduction of different aryl groups at the 3- and 4-positions was found to be feasible. These procedures were successfully applied for the total syntheses of lamellarin G trimethyl ether, lamellarins D,L,and N. Formal syntheses of permethyl storniamide A and ningalin B were also achieved.
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