5′-Nor Carbocyclic 5′-Deoxy-5′-(Isobutylthio)Adenosine and a 2′,3′-Dideoxy-2′,3′-Didehydro Derivative

Abstract

The inhibition of biochemical processes requiring S-adenosylmethionine as a co-factor have led to many nucleoside-based medicinal agents. Included in this group are 5′-deoxy-5′-(isobutylthio)adenosine (SIBA), a nucleoside with antiparasitic, antiviral and antiproliferative effects, and 5′-noraristeromycin, a carbocyclic-derived nucleoside with potent antiviral properties. This report brings together the structural components of these two compounds by describing both enantiomers of carbocyclic 5′-nor SIBA (3 and 4). Owing to the recent interest in 2′,3′-dideoxy-2′,3′-didehydro nucleosides as antiviral agents, this derivative of 3 (5) is also described. All three compounds were screened against a variety of viruses and were found to be inactive at high concentrations or at limiting concentrations for the screening methods. The viruses subjected to 3–5 were herpes simplex virus types 1 and 2, human cytomegalovirus, vaccinia virus, vesicular stomatitis virus, respiratory syncytial virus, varicella zoster virus, coxsackie virus, parainfluenza-3 virus, sindbis virus, punta toro virus, reovirus-1, human immunodeficiency virus, influenza virus types A and B, adenovirus type 1 and measles virus. These results suggest that the C-5′ methylene of the C-5′ thio-based carbocyclic nucleosides is important for their antiviral properties.