Synthesis and Biological Evaluationof 6-Substituted Purinylcarbanucleosides with a Cyclopenta[<i>b</i>]thiophene Pseudosugar

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).