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Synthesis 2009(16): 2766-2772  
DOI: 10.1055/s-0029-1216908
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis and Biological Evaluation of 6-Substituted Purinylcarbanucleosides with a Cyclopenta[b]thiophene Pseudosugar

Paula Abeijóna, José M. Blanco*a, Olga Caamañoa, Franco Fernándeza, Marcos D. Garcíab, Xerardo García-Meraa, José E. Rodríguez-Borgesc, Jan Balzarinid, Erik De Clercqd
a Departamento de Química Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax: +34(981)594912; e-Mail: jm.blanco@usc.es ;
b Departmento de Química Fundamental, Facultade de Ciencias, Campus da Zapateira s/n, 15701 A Coruña, Spain
c CIQ, Departamento de Química, Facultade de Ciencias do Porto, Rua do Campo Alegre, 687-4169007 Porto, Portugal
d Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Further Information

Publication History

Received 16 April 2009
Publication Date:
14 July 2009 (online)

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Abstract

The first members of a new family of heterocarbobicyclic nucleoside analogues have been synthesized from the cis/trans mixture of (4-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-6-yl)methanols (cis/trans -7). The separation of the cis and trans intermediates during the preparation of the 6-chloropurine derivatives allowed a separate preparation of the purine heterocarbanucleosides cis-10 and trans-11, from which cis-12-14 and trans-16-18 were obtained by replacement of the 6-chloro substituent with amino, hydroxy, and cyclopropylamino groups. Additionally, the 6-phenylpurinyl analogues cis-15 and trans- 19 were prepared from cis-10 and trans-11 using Suzuki-Miyaura methodology. In tests of antiviral and cytostatic activities, compound 11 showed cytostatic activity against Molt4/C8 human T lymphoblastic leukemia cells. Antiviral activity was shown by compounds 15 and 19 against Punta­ Toro virus and Coxackie virus B4 (compound 11).

Key words

heterobicyclic amino alcohol - cyclopenta[b]thiophene - Suzuki-Miyaura cross-coupling reaction - purinylcarbanucleoside - biological activity

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CCDC-636456 contains the supplementary crystallographic data for compound trans-18 reported in this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.