The synthesis of 6¡ä-methyl-5¡ä-homoaristeromycin is described from a known 6¡ä-ethyl ester. Antiviral analysis showed the (S)-6¡ä stereoisomer retained the vaccinia activity of the parent 5¡ä-homoaristeromycin (1) while the (R)-6¡ä isomer was less active. Both were weaker than 1 towards cowpox. The diastereomers were equally active versus Epstein Barr virus while (S)-6¡ä was three times more active toward vesicular stomatitis virus than (R)-6¡ä. The diastereomers were inactive towards numerous other viruses. The CC50 for both diastereomers was >300 ¦ÌM.