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The 1′,6′-isomer of neplanocin A possesses biological properties that have not been optimised through rationally conceived analogues. In that direction, this Letter reports the use of the Ullmann reaction to achieve enantiomeric 3-deaza-1′,6′-isoneplanocin and 3-bromo-3-deaza-1′,6′-isoneplanocin. These four compounds showed significant Ebola activity that is not specifically due to their inhibition of S -adenonosylhomocysteine hydrolase, as might have been expected for 3-deazaadenine carbocyclic nucleosides. For some members of this group, antiviral activity was also found against human cytomegalovirus, hepatitis B, norovirus, and measles. [ABSTRACT FROM AUTHOR]

Synthetically combining the C-4′ side-chain structural features of the antiviral candidates 5′-methylaristeromycin and 5′-homoaristeromycin into a diastereomeric pair of C-4′ side-chain dihydroxylated aristeromycins ( 6 and 7 ) is reported. Broad antiviral analyses of the both targets found promising effects towards HBV ( 6 , 6.7 μM and 7 , 7.74 μM) and HCMV (only 7 , 0.72 μM). No other activity was found. Neither of the diastereomers was cytotoxic in the assays performed. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract A convenient stereospecific synthesis of 6′-fluoro-3-deazaneplanocin (6) has been accomplished from d -ribose in 15 steps. It is reported to possess significant activity towards Ebola (Zaire, Vero, μM: EC 50 < 0.36; CC 50 125; SI > 347) with moderate inhibition of the target enzyme (S-adenosylhomocysteine hydrolase), which did not correlate directly with its anti-Ebola effects. Compound 6 , with limited cytotoxicity, also displayed activity against measles, H1N1 and Pichinde. [ABSTRACT FROM AUTHOR]