Semisynthesis of heterocyclic analogues of squamocin, a cytotoxic annonaceous acetogenin, by an unusual oxidative decarboxylation reaction.
In addition to two expected pyrazin derivatives, two imidazole analogues of squamocin 1 have been semisynthetised from squamocin derived alpha-ketoesters/alpha-ketoacid, via an unusual condensation-oxidative decarboxylation reaction with 1,2 diamines in presence of acetic acid and oxygen as the key step. Some of these analogues exhibited potent, although significantly reduced cytotoxicities relatively to squamocin 1. In addition, benzimidazole 8 possessed in comparison with the natural acetogenin some interesting cell cycle effects.
Duval
R
R
Laboratoire de Pharmacognosie (BioCis, UMR 8076 CNRS), Faculté de Pharmacie, rue J. B. Clément, 92296 Cedex, Châtenay-Malabry, France.
Lewin
G
G
Hocquemiller
R
R
D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003653:Decarboxylation; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D010084:Oxidation-Reduction
D005663:Furans; D007783:Lactones; C059660:squamocin