1992 Fiscal Year Final Research Report Summary
Synthesis of Anti-viral Carbocyclic Nucleosides Using Selective Photo-cycloadditions
| Project/Area Number |
03805079
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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 |
Synthetic chemistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
SHIMO Tetsuro Kagoshima Univ., Fac. of Eng., Associate Professor, 工学部, 助教授 (80041565)
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| Co-Investigator(Kenkyū-buntansha) |
MURAOKA Fumiko Kagoshima Univ., Fac. of Eng., Assistant, 工学部, 教務職員 (90229948)
UEMURA Hisako Kagoshima Univ., Fac. of Eng., Research Associate, 工学部, 助手 (20041535)
SOMEKAWA Kenichi Kagoshima Univ., Fac. of Eng., Professor, 工学部, 教授 (10041534)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Photoaddition / 2-Pyrone / 2-Pyridone / Cyclobutanes / Carbocyclic Nucleoside / Antivirus / Aids |
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| Research Abstract |
We studied many kinds of photo-[2+2]cycloaddition reaction and analyzed factors of the addition selectivity. We next utilized the proper adducts for synthesis of cyclobutanecarbocyclic nucleosides having exhibited potent anti-AIDS-viral activities as follows.
1. The skeleton of 2-pyrones is a simple one composed of 2,4-cyclohexadienones. To elucidate the peri-, site- and regioselective [2+2]photoadditions (cyclobutane-formations) of the triplet 2-pyrones with some ethylenes, the factors were analyzed by PM3-CI-UHF method.
2. Site, regio- and stereoselective cyclobutane-formations of 2-pyridones' singlet and triplet photoadditions were also investigated and were inferred to come from their frontier orbital interactions and polar effects.
3. Many kinds of (omega-alkenyl)-2-pyrones and -2-pyridones were prepared and their photosensitized cycloadditions afforded tricyclic cyclobutanes. We also analyzed their factors of those selective additions.
4. Photoreaction of maleic anhydride with vinyl acetate gave a preferable product 3-acetoxycyclobutane-1,2-dicarboxylic acid (1), whose configuration was all-cis. Esterification of 1 with diazomethane gave desired dimethlyl 3-acetoxycyclobutane-1,2-dicarboxylate (2). Coupling of 2 with adenine as a nucleic acid using potassium carbonate affroded 6-amino-9-[2,3-bis(methoxycarbonyl)cyclobutanyl]purine (3) which had desired all-trans configuration. The all-trans configuration of 3 was inferred by the NOE data of cyclobutane ring. Reduction of 3 with lithium aluminum hydride gave 6-amino-9-[2,3-bis(hydroxymethyl)cyclobutanyl]purine (4) having exhibiled potent anti-AIDS-viral activities. The sysnthesis of 4 was achieved through only 4 steps. It is the shortest process.
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