Synthesis of acronycine isosters

Abstract

The synthesis of the two key intermediates 6,8-dihydroxy-10-methylbenzo[b][1,8]naphthyridin-5(10H)-one (4b) and 6,8-dihydroxy-5H-[1]benzopyrano[2,3-b]pyridin-5-one (4d) for the synthesis of acronycine isosteres is described. The condensation of (4b) with 3-chloro-3-methylbut-1-yne afforded three isomers (5), (6), and (7), from which it was possible to distinguish between the angular isomer (5) and the linear isomer (6) with the aid of ¹³C n.m.r. spectroscopy. The condensation of (4d) with 3-chloro-3-methylbut-1-yne yielded only one product (8). The action of dimethyl sulphate on 6-hydroxy-3,3-dimethyl-3H-pyrano[2′,3′ : 7,8]chromeno[2,3-b]pyridin-7-one (8) as well as on 6,8-dimethoxy-5H-[1]benzopyrano[2,3-b]pyridin-5-one (3b) is also reported.