(6'R)- and (6'S)-6'-C-methyl-3-deazaneplanocin A's were synthesized from D-dose as anti-RNA virus agents. Of these compounds, (6'R)-6'-C-methyl-3-deazaneplanocin A (4b) showed the greatest anti-RNA virus activity in vitro. It was found that the 6'R-configuration was essential for the antiviral activity of 6'-C-methylneplanocin A derivatives.Neplanocin A (NPA, l)* has a broad-spectrum antivirus activity due to its inhibitory effect on cellular S-adenosylhomocysteine (AdoHcy) hydrolase,3 which regulates biologically important methylation processes4 However, NPA itself also showed apparent cytotoxicity to host cells.5 It has been recognized that the detrimental toxicity of NPA could be derived, for the most part, from phosphorylation of the primary hydroxyl group at its 6'-position by adenosine kinase and subsequent metabolism by cellular enzymes.5 Consequently, to remove or reduce such side effects, much attention has been focused on chemical modification of NPA.6We recently reported the synthesis of (6'R)- and (6'S)-6'-C-methylneplanocin A's (RMNPA 3b and SMNPA 3a, respectively) from NPA, which were designed not to be phosphorylated due to steric hindrance of the methyl group but still to have inhibitory effect on AdoHcy hydrolase, and found that one of the diastereomers showed significant antiviral activity against various pathogenic viruses such as parainfluenza, respiratory syncytial, measles, and cytomegalo viruses, without considerable cytotoxicity toward host cells.7 However, the 6' configurations of each diastereomer have not been confirmed.In this communication, we describe synthesis of (6'R)- and (6'S)-6'-C-methyl-3-deaza-NPA's (4b and 4a, respectively) as another example of non-cytotoxic antiviral agents and identification of the 6' configurations at the 6'-position of 3 and 4.