1990 Fiscal Year Final Research Report Summary
Synthesis of Tetronic Acid Containing Ionophore Antibiotics
| Project/Area Number |
01571144
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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 | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
YOSHII Eiichi Toyama Med. Pharm. Univ., Fac. Pharm. Sci., Professor, 薬学部, 教授 (50019105)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Kozo the same as above, assistant, 薬学部, 助手 (50173612)
TAKEDA Kei the same as above, Lecturer, 薬学部, 講師 (30135032)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Tetronomycin / Tetronasin / Ionophore Antibiotic / Synthesis / Aldol Reaction / Allylation |
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| Research Abstract |
The polyether ionophore antibiotics, tetronomycin and tetronasin discovered in early 1980s by Swiss Sandoz and ICI, respectively, have the novel structures in which strongly acidic acyltetronic acid group is attached as metal cation trapping functionality instead of carboxylic group found with usuall natural ionophores. Interests in the molecular architectures as well as their biological activities have called for intensive synthetic investigation in several laboratories. We have now achieved the first total synthesis of tetronomycin as outlined below.
1. Synthesis of the polyether fragment.
The two oxygenーcontaining heterocycles that consist of the polyether group were prepared : (2-methoxy) tetrahydrofuran fragment from L-rhamnose, and (tetrahydropyranー2-yl) allysilane from L-ascorbic acid or (R)-3-hydroxyisobutyrate. Reaction of the two components in the presence of boron trifluoride aforded the polyether fragment of the correct stereochimistry in high yield.
2. Synthesis of the functionalized cyclohexane fragment.
An improved synthetic method involving L-Selectrideーmediated reductive cyclization of 1,7-heptadieneー1,7-dicarboxylate has been introduced.
3. Total synthes is of tetronomycin.
Aldol reaction of the cyclohexane fragment with the ployether fragment bearing terminal (methoxycarbonyl) methyl group followed by photoisomerization of the resulーting conjugated ester provided the linear threeーring system, which was coupled with gammaーmethylene beta-tetronate to give tetronomycin after removal of protecting groups.
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