1986 Fiscal Year Final Research Report Summary
The Enantioselective Synthesis of Some Useful Antibiotics based on the Chemicoenzymatic Strategy.
| Project/Area Number |
59430024
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, University of Tokyo |
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Principal Investigator |
OHNO Masaji Faculty of Pharmaceutical Sciences, Univ. of Tokyo, Professor, 薬学部, 教授 (00111550)
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| Project Period (FY) |
1984 – 1986
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| Keywords | Pig liver esterase / Synthesis of antibiotics / Symmetrization-asymmetrization concept / Retrosynthesis / Fortimicine / リゾチシン |
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| Research Abstract |
Since 1978, we have begun to synthesize biologically active natural products by a reasonable combination of enzymatic process (pig liver esterase, PLE) and usual organic synthesis and developed a new avenue for natural product synthesis. Our synthetic strategy for obtaining various antibiotics has therefore been designed as follows.
(1) Retrosynthesis is performed to generate, from the target molecule, a symmetric diester in the prochiral or meso form.
(2) The symmetric diester is subjected to asymmetric hydrolysis with pig liver esterase to generate the corresponding chiral half-ester. (enzymatic conversion of <sigma> -symmetry to <C_1> -symmetry)
(3) The chiral half-ester is converted to the target molecule by means of organic synthesis. The total strategy is called "Symmetrization-asymmetrization Concept".
Thus, in addition to various carbapenem antibiotics and nucleosides, fortimicin A and part of rhizoxin were synthesized and the results were presented at various famous international meetings of the world.
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