A new synthetic access to furo[3,2-f]chromene analogues of an antimycobacterial.

Luke Alvey (1) , Soizic Prado (2) , Valérie Huteau (1) , Brigitte Saint-Joanis (3) , Sylvie Michel (4) , Michel Koch (4) , Stewart T Cole (3) , François Tillequin (4) , Yves L Janin (1)

1 Chimie Organique
2 Laboratoire de chimie et biochimie des substances naturelles
3 Génétique Moléculaire Bactérienne
4 UMR 8638 - Equipe Pharmacognosie

From the structure of 3,3-dimethyl-3H-benzofuro[3,2-f][1]-benzopyran, a selective in vitro inhibitor of mycobacterial growth, we have undertaken a structure-activity relationship investigation. We wish to report here our results on the use of [2+3] cycloadditions between 2-formylbenzoquinone and various enol derivatives to give various 4-formyl-5-hydroxy benzofurans. In the next step, an ytterbium triflate-catalysed reaction with 2-methylpropene allowed the preparation of various original furo[3,2-f]chromenes derivatives. Their biological evaluation on the growth of Mycobacterium smegmatis as well as Mycobacterium tuberculosis pointed out that some analogues were four times more active than the initial hit.

Domains: Life Sciences [q-bio]; Microbiology and Parasitology

Luke Alvey, Soizic Prado, Valérie Huteau, Brigitte Saint-Joanis, Sylvie Michel, et al.. A new synthetic access to furo[3,2-f]chromene analogues of an antimycobacterial.. Bioorganic and Medicinal Chemistry, 2008, 16, pp.8264-8272. ⟨10.1016/j.bmc.2008.06.057⟩. ⟨pasteur-00315963⟩