Pyrano[2,3-e]isoindol-2-ones, new angelicin heteroanalogues

A convenient synthesis of the pyrano[2,3-e]isoindol-2-one ring system, an heteroanalogue of angelicin, is reported. Our synthetic approach consists of the annelation of the pyran ring on the isoindole moiety using 5-dialkylamino- or 5-hydroxymethylene intermediates as building blocks. The photoantiproliferative activity of the new derivatives was studied. Some of them bearing the benzyl group at the 8 position were active with IC50 in the micromolar range. Cell cytotoxicity involves apoptosis, alteration of cell cycle profile and membrane photodamage.

Graphical abstractA versatile and convenient pathway for the synthesis of pyrano[2,3-e]isoindol-2-one derivatives and their photochemotherapeutic activity are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide