Tetracyclic eudistomins 1, which were isolated out of the colonial turnicate Eudistomin olivaceum, possessed very potent antiviral and antitumor activities.
We have developed the synthesis of oxazepinopyridoindoles 2, which are corresponding to the carba analogs of natural eudistomins, via Meisenheimer rearrangement of azetopyridoindoles 4. For the structure activity relationship investigation of 1,12-carbaeudistomin analogs 3 were synthesized from 4 and their antiviral activities against influenza A and B virus, HSV-1, HSV-2, and human cytomegalovirus were evaluated. Among them, racemic 6-methoxy-12-carba- eudistomin 5 having beta-amino group has exhibited almost the same order activity as that of (-) -debromoeudistomin K,synthesized as a control compound. Also MNDO calculation showed that the conformation of the carbaeudistomins is very similar to that of natural eudistomins.
These results clearly indicate that the oxazepine ring in the carbaeudistomins is equivalent to the oxathiazepine ring in the natural eudistomins for the antiviral activities.