Synthesis and antiviral activity of carbocyclic oxetanocin analogues (C-OXT-A, C-OXT-G) and related compounds. II.

9-(cis-3-Hydroxymethyl-2-methylenecyclobutyl)guanine (3b) and 9-(3-methylene-trans-2-hydroxymethylcyclobutyl)guanine (4b) were prepared from N2-isobutyryl-9-[trans-trans-2,3-bis(hydroxymethyl)cyclobutyl]guanine (2f) or 2,3-bis(hydroxymethyl)-1-cyclobutanol (7b). Carbocyclic oxetanocin analogues (A, 1d; G, 2d) and related compounds including 4b were assayed against a broad variety of viruses. It appeared that the activity of 2d against herpes simplex virus (HSV) and varicella-zoster virus (VZV) at least partially depends on phosphorylation by the virus-induced thymidine kinase (TK). Although 1d and 2d are inhibitory to the replication of human immunodeficiency virus (HIV), they are quite toxic to proliferating human T-lymphocytes.