1994 Fiscal Year Final Research Report Summary
Synthetic Studies Toward Antitumor Antibiotic Fredericamycin A,HavingUnique Spiro Ring System
| Project/Area Number |
05671757
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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 |
Chemical pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
WATANABE Mitsuaki Nagasaki University, Center for Instrumental Analysis, Associate Professor, 計測・分析センター, 助教授 (10039654)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Fredericamycin A / Dimethyl Phthalide-3-phosphonate / Lithiation Reaction / Wittig-Horner Reaction |
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| Research Abstract |
The structure of Fredericamycin A is sufficiently complex that a total synthesis is not a simple undertaking. However, the development of synthetic route to Fredericamycin A could prove to be a medically useful achievement because Fredericamycin A is a very powerful antitumor agent.
The investigator succeeded in development of following useful synthetic reaction for Fredericamycin A.
1) A Regioselective Synthesis of Dimethyl Phthalide-3-phosphonates : Dimethyl phthalide-3-phosphonates, hving various substituents on the benzene ring, were regioselectively synthesized by the reaction of N,N-diethyl-2-formylbenzamides with tert-butyldimethylsilyl dimethyl phosphite followed by treatment with methanesulfonic acid.
2) An Annulation Reaction Using Dimethyl Phthalide-3-phosphonates : A variety of naphthalene-1,4-diol derivatives were regioselectively synthesized by the annulation reaction with electron-deficient olefins.
3) Synthesis of the BCDE Ring Part of Fredericamycin A : Wittig-Horner reaction of dimethyl phthalide-3-phosphonates with 1-indanones in the presence of LHMDS to give the 3- (1'-indanylidene) phthalides in good yields. The above indanylidenephthalides were transformed into dibenzo-1,4-diketospiro [4,4] nonanes, the BCDE ring system of Fredericamysin A,by consecutive treatment with DIBAL and PDC.
4) Synthesis of the ABCDE Ring Part of Fredericamycin A : The annulation reaction of dimethyl phthalide-3-phosphonates with 2 (5H) -furanone gave highly functionalized-benzophthalides in good yields. The above benzophthalides were converted to the dimethyl benzophthalide-3-phosphonates by two steps. The construction of the ABCDE ring system of Fredericamycin A was achieved by the Wittig-Horner reaction of dimethyl benzophthalide-3-phosphonates with 2 (5H) -furanones as a key reaction.
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