Synthesis and Biological Evaluation of 6-Substituted Purinylcarbanucleosides with a Cyclopenta(6)thiophene Pseudosugar

摘要

The first members of a new family of heterocarbobicy-clic nucleoside analogues have been synthesized from the cisltrans mixture of (4-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-6-yl)methanols (cisltrans-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 cw-12-14 and trans-16-18 were obtained by replacement of the 6-chloro substituent with amino, hy-droxy, and cyclopropylamino groups. Additionally, the 6-phe-nylpurinyl analogues cis-15 and trans-19 were prepared from cis-W and trans- 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).