1995 Fiscal Year Final Research Report Summary
Shynthesis of Carbocyclic Nucleosides Having Biological Function
| Project/Area Number |
06672230
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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 |
医薬分子機能学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
KATAGIRI Nobuya Tohoku Univ. Pharmaceutical Institute, associate, Professor, 薬学部, 助教授 (60089787)
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| Co-Investigator(Kenkyū-buntansha) |
TOYOTA Akemi Tohoku University, Pharmaceutical Institute, Instructor, 薬学部, 教務職員 (80237148)
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| Project Period (FY) |
1994 – 1995
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| Keywords | carbocylic nucleoside / nitrone / anti-HIV activity / bicyclic amide / asymmetric synthesis / cis-difluoro compound / Diels-Alder reaction / adenosine deaminase |
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| Research Abstract |
1. The cis-dihydroxylation of cis-3,5-disubstituted cyclopentenes leading to carbocyclic nucleosides was examined. Its stereoselectivity was found to be attibutable to the conformation of substituents of cyclopentenes.
2. Addition of molecular fluorine to bicyclo [2.2.1] hept-2-ene derivatives and conversion to fluorine-containing carbocyclic nucleosides were carried out. Biological evaluation of these nucleosides did not show any anti-HIV activity.
3. Asymmetric hetero Diels-Alder reaction of benzenesulfonyl cyanide with cyclopentadiene using chiral Lewis acids was investigated to give opticaliy active 2-azabicyclo [2.2.1] hept-5-en-3-one, which was a synthon of chiral carbocyclic nucleosides.
4. The 1,3-dipolar cycloaddition reaction of bornadiene or bicycloamides with cyclic nitrones obtained from nitrosoketene with ketones gave stereoselectively the exocycloadducts, which would be intermediates for the synthesis of carbocyclic nucleosides containing an alpha-amino acid residue.
5. A new dienophile, dimethyl trifluoroacetylaminomethylenemalonate, was created. The dienophile reacted readily with cyclopentadiene to give a bicyclic compound leading to carbocyclic homo-nucleosides.
6. Deamination of carbocyclic adenine nucleosides by adenosine deaminase under highpressure revealed that the deamination was a useful procedure for the kinetical resolution of racemic carbocyclic nucleosides.
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