1‐Deaza‐5′‐noraisteromycin

Abstract

(±)‐1‐Deazaaristeromycin (4) has been reported to be an inactivator of S‐adenosylhomocysteine (AdoHcy) hydrolase and, as a consequence, to affect S‐adenosylmethionine (AdoMet) mediated macromolecular biomethylations. To extend this to our program focused on 5′‐noraristeromycin derivatives as inhibitors of the same hydrolase enzyme as potential antiviral agents, both enantiomers of 1‐deaza‐5′‐noraristeromycin (5 and 20) have been prepared. Compounds 5 and 20 were evaluated against the following viruses: vaccinia, cowpox, monkeypox, Ebola, herpes simplex type 1 and 2, human cytomegalovirus, Epstein Barr, varicella zoster, hepatitis B, hepatitis C, HIV‐1 and HIV‐2, adenovirus type 1, measles, Pichinde, parainfluenza type 3, influenza A (H1N1 and H3N2), influenza B, Venezuelan equine encephalitis, rhinovirus type 2, respiratory syncytial, yellow fever, and West Nile. No activity was found nor was there any cytotoxicity to the viral host cells.

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

Keywords:

• 1‐Deazaaristeromycin
• AdoHcy
• AdoMet

Acknowledgments

This research was supported by funds from the Department of Health and Human Services (AI 48495 and AI 56540), which is appreciated. We would also like to thank Dr. Erik De Clercq, the Rega Institute, Leuven Belgium; Dr. Earl Kern, University of Alabama at Birmingham, Birmingham, AL; Dr. Brent Korba, Georgetown University, Washington, DC; Dr. Robert Sidwell, Utah State University, Logan, UT; and Drs. John Huggins and Chris Whitehouse of the U.S. Army Medical Research Institute of Infectious Diseases for the antiviral testing.

Notes

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

^aEnantiomeric purity was determined by proton NMR spectroscopy in the presence of the chiral shift reagent tris[3‐(heptafluoropropylhydroxymethylene)‐d‐camphara]europium (III), Eu(hfc)₃.