1989 Fiscal Year Final Research Report Summary
Studies on the Synthesis of the Fluorescent Hypermodified Nucleoside.
| Project/Area Number |
63570988
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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 | Kanazawa University |
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Principal Investigator |
ITAYA Taisuke Kanazawa University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20019657)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Transfer ribonucleic acid / Hypermodified nucleoside / Fluorescent nucleoside / Optically active beta, gamma-unsaturated amino acid / Vinylglycine / Chiral synthesis / Heck reaction / High-performance liquid chromatography |
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| Research Abstract |
We had already achieved the synthesis of wybutine, the base of the title compound, wybutosine, by means of the Wittig or the, Heck reaction as a key step. Neither similar Wittig approach nor the modified procedure effected the synthesis of our target compound, 3-beta-D-ribofuranosylwye (1). On the other hand, the Heck reaction at the nucleoside level successfully afforded 1. This product, however, proved to be contaminated by its diastereomer. In order to develop a stereoselective synthesis of 1, we attempted several recent methods of C-C bond forming reactions as well as modification of the Heck reaction. Because none of them gave a positive result, we focused on separation of (S)-4,9-dihydro-alpha-[(methoxycarbonyl)amino]-4,6-dimethyl-9-oxo-3-(2,3,5-tri-omicron-acetyl-beta- D-ribofuranosyl)-3H-imidazo[1,2-alpha]purine-7-butanole acid (2), a precursor for the synthesis of 1, from its diastereomer by high-performance liquid chromatography. The separation was attained by use of a reversed-phase system [acetonitrile-0.02 M aqueous sodium dihydrogen phosphate (15:85, v/v)]. Compound 2 was treated with trimethyl- silyldiazomethane followed by deacetylation to afford stereochemically pure I for the first time. Compound 1 thus obtained underwent unusually fast hydrolysis at the N-glycosidic bond and the rate was of the same order of magnitude as that reported for wybutosine. Because 2',3',5'-tri-omicron-acetyl derivative of 1 proved much more stable than 1, isolation and identification of wybutosine should be done through its triacetate.
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Research Products
(4 results)
