Bernadette Hugon

Synthesis of isogranulatimide analogues possessing a pyrrole moiety instead of an imidazole heterocycle

An efficient four step synthesis from commercial indoles of isogranulatimide analogues is reported. In the new compounds, the imidazole moiety is replaced by a pyrrole unit, the indole part is substituted or not in 5-position and the nitrogen of the imide moiety bears or not a methyl substituent.

Synthesis of isogranulatimides A and B analogues possessing a 7-azaindole unit instead of an indole moiety

The synthesis of a new family of isogranulatimides analogues is described in which a 7-azaindole replaces the indole moiety. The key step is the photocyclization of the aza didemnimide intermediates which leads to two isomeric analogues of isogranulatimides A and B. A derivative bearing a carbohydrate part linked to the azaindole via a β-N-glycosidic bond was also prepared.

Synthesis of granulatimide analogues bearing a maleimide instead of an imidazole heterocycle

A synthesis in a few steps of a new family of granulatimide analogues was performed. In the new compounds, the aromatic framework of granulatimide is modified by replacement of the imidazole unit by a maleimide moiety. The synthesis of a water-soluble analogue is also presented.

Pyrrolocarbazoles as Checkpoint 1 Kinase Inhibitors

The carbazole framework is found in many natural compounds of biological interest. Indolocarbazoles such as rebeccamycin and staurosporine which are either a topoisomerase I inhibitor (rebeccamycin) or a non selective kinase inhibitor (staurosporine) are bacterial metabolites. In the search for new antitumor agents, DNA damage checkpoint kinases, in particular Checkpoint kinase 1, have recently emerged as attractive targets for cancer therapy. This review reports the synthesis and Chk1 inhibitory activities of pyrrolocarbazole compounds bearing four or five fused rings.