Synthesis of 3-Deazaneplanocin A, a Powerful Inhibitor of S-Adenosylhomocysteine Hydrolase with Potent and Selective in Vitro and in Vivo Antiviral Activities

Article abstract of DOI:10.1021/jm00127a007

The neplanocin A analogue 3-deazaneplanocin A (2b) has been synthesized.A direct S_N2 displacement on the cyclopentenyl mesylate 3 by the sodium salt of 6-chloro-3-deazapurine afforded the desired regioisomer 4 as the major product.After deprotection, this material was converted to 3-deazaneplanocin A in two steps.X-ray crystallographic analysis confirmed the assigned structure.Consistent with its potent inhibition of S-adenosylhomocysteine hydrolase, 3-deazaneplanocin A displayed excellent antiviral activity in cell culture against vesicular stomatitis, parainfluenza type 3, yellow fever, and vaccinia viruses.Antiviral activitiy was also displayed in vivo against vaccinia virus by using a mouse tailpox assay.The significantly lower cytotoxicity of 3-deazaneplanocin A, relative to its parent compound neplanocin A, may be due to its lack of conversion to 5'-triphosphate and S-adenosylmethionine metabolites.