Synthesis of New Furo[3,4-b]quinolin-1(3H)-one Scaffolds Derived from [gamma]-Lactone-Fused Quinolin-4(1H)-ones

In the context of our aim of discovering new antitumor drugs among synthetic [gamma]-lactone- and [gamma]-lactam-fused 1-methylquinolin-4(1H)-ones, we developed a rapid access to 5-methyl-1,3-dioxolo[4,5-g]furo[3,4-b]quinoline-8,9(5H,6H)-dione (9) exploiting the [gamma]-lactone-fused chloroquinoline 10 previously synthesized in our laboratory (Scheme1). We also elaborated efficient synthetic methods allowing for a rapid access to two nonclassical bioisosteres of 9, i.e., a deoxy and a carba analogue. The deoxy analogue 11 was prepared in two steps from the [gamma]-lactone-fused quinoline 13 which was also the synthetic precursor of 10 (Scheme1). The carba analogue 6,9-dihydro-5-methyl-9-methylene-1,3-dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one (12) was easily prepared by HCl elimination from the 9-(chloromethyl)dioxolofuroquinoline 15, which was obtained via a three-component one-pot reaction from N-methyl-3,4-(methylenedioxy)aniline (=N-methyl-1,3-benzodioxol-5-amine; 16), commercially available chloroacetaldehyde, and tetronic acid (17) (Scheme2). [PUBLICATION ABSTRACT]