Total synthesis of structures proposed for quinocitrinines A and B and their analogs. Microwave energy as efficient tool for generating heterocycles

A first total synthesis of the structures proposed for quinocitrinines A and B has been accomplished by a three steps strategy which also applies for the synthesis of non-natural analogs. In the first step a microwave assisted Friedlander condensation between a substituted oamino-benzaldehyde and a substituted tetramic acid generated intermediate fused tricyclic quinolines which were N-methylated using methyl triflate. The natural compounds were obtained after cleavage of an O-methyl group from the aryl ring using BBr ₃. All the reactions were affected by epimerization of the C-11 in the lactam ring which converted quinocitrinine A into quinocitrinine B. In order to diminish epimerization, optimization assays were necessary. Extensive NMR analysis of the synthetic compounds and their lack of biological activity as compared to those of the previously isolated natural products, revealed that the structures of the natural products remain to be elucidated.