Alexandra Kamlah and Franz Bracher* Pages 1 - 4 ( 4 )
A new synthesis of the 2,6-naphthyridine alkaloid 4-methyl-2,6-naphthyridine from Antirrhinum majus has been developed. Key steps are a regioselective oxidation of 3-bromo-4,5- dimethylpyridine to the corresponding 4-formyl derivative, and the annulation of the second pyridine ring by Suzuki-Miyaura cross-coupling using (E)-2-ethoxyvinylboronic acid pinacol ester as a masked acetaldehyde equivalent. This protocol gives the alkaloid in four steps starting from commercially available 3,4-dimethylpyridine in 15% overall yield. This annulation protocol should be useful for the synthesis of other condensed pyridines as well.
alkaloid, naphthyridine, oxidation, annulation, Suzuki-Miyaura coupling, enol ether
Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians University, Butenandtstr. 5-13, 81377 Munich, Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians University, Butenandtstr. 5-13, 81377 Munich