1992 Fiscal Year Final Research Report Summary
Studies towards the Synthesis of the Hypermodified Nucleoside Isolated from Mammalian Transfer Ribonucleic Acids and Its Isotopically Labelled Compounds.
| Project/Area Number |
03670997
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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) |
1991 – 1992
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| Keywords | Hypermodified nucleoside / Fluorescent nucleoside / Optically active beta,gamma-unsaturated amino acid / Wittig reaction / Heck reaction / Cyclic carbonate / Oxalyl chloride / Stereoelectronic effect |
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| Research Abstract |
The synthesis of the title compounds involves the Witting reaction or the Heck reaction, and transformation of the 1,2-diol compound to the cyclic carbonate, as the key steps. Although the Witting reaction using (R)-[2-carboxy-2-[(methoxycarbonyl)amino]ethyl]triphenylphosphonium chloride (1) had not afforded the desired product at the nucleoside level, we obtained the key intermediate by employing 7- formyl-3-[2,3,5-tri-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]wye and the inner salt 2 derived from 1. We also demonstrated that the product obtained in the Wittig reaction between 2 and piperonal was optically pure. For the synthesis of compounds labelled with an isotope, several phosphonium salts (type 2) differently protected at the amino group were synthesized. Among them benzyloxycarbonyl and tert-butoxycarbonyl compounds gave positive results in the Wittig reaction with piperonal; the former was better in view of the yield. On the other hand N-(tert-butoxycarbonyl)vinylglycine was better than the benzyloxycarbonyl compound for the Heck reaction with 1-benzyl- 7-iodowye. Thus we established two stereoselective methods of preparing optically active (E)-(2-arylvinyl)glycine derivatives.
It was necessary for us to elucidate the mechanism of the formation of the cyclic carbonates in the reaction of 1,2-glycols and oxalyl chloride for improvement of the yield of the target nucleosides. We then studied the reactions of oxalyl chloride with various 1,2- glycols; the results allow us to explain the formation of the carbonates in terms of stereoelectronically controlled cleavage of the tetrahedral intermediates. According to the proposed mechanism we may have a chance of finding how to prepare exclusively the carbonates or the oxalates, whichever we want. Further investigation along this line is under progress.
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