Enantiomeric 4'-Truncated 3-deaza-1',6'-isoneplanocins: synthesis and antiviral properties including Ebola

Abstract Enantiomeric 3-deaza-1',6’-isoneplanocins (C-3 unsubstituted 7a / 7b and C-3 with a bromine 8a / 8b ) lacking the 4'-hydroxymethyl as mechanistically designed anti-viral targets have been prepared by utilizing the Ullmann reaction. Anti-Ebola properties were found for the D-like 7a and 8a and L-like 8b . All four products showed effects against human cytomegalovirus while D-like 7a / 8a affected measles; 7a was effective versus norovirus and 8a inhibited Pichinde. Both 7a and 8a produced SAHase inhibitory effects. However, the anti-EBOV activity of 7a and 8a cannot be readily correlated with this observation due with their contrasting IC 50 values ( 8a > 7a ). It is to be noted that 7b showed no effects on this enzyme and 8b was minimally inhibitory. These results offer preliminary insight into the differing mechanisms of action of D- and L- like structures and enlighten structural features to guide additional antiviral agent pursuit in the isoneplanocin series