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

• Published in: Synthesis (Stuttgart) 2009-08, Vol.2009 (16), p.2766-2772
• Main Authors: Abeijón, Paula, Blanco, José M., Caamaño, Olga, Fernández, Franco, García, Marcos D., García-Mera, Xerardo, Rodríguez-Borges, José E., Balzarini, Jan, De Clercq, Erik
• Format: Article
• Language: English
• ISSN: 0039-7881; 1437-210X
• DOI: 10.1055/s-0029-1216908

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).