An Isomerization Approach to Tesirine and Pyrrolobenzodiazepines

The isomerization of a pyrrolobenzodiazepine (PBD) containing an exo-alkene to one containing an endo-alkene has been demonstrated to prepare a key intermediate for the synthesis of tesirine. This methodology has afforded a shorter formal synthesis of tesirine, delivering a 24-step route compared to the previously reported shortest route of 29 steps. It is anticipated that this methodology will have broader application for converting other PBDs containing exo-alkenes to those containing endo-alkenes.