Cyclocondensation of 3-acetylfuran-2(5H)-ones with benzylidenemalononitrile. Synthesis of 3-(5-amino-4,6-dicyanobiphenyl-3-yl)furan-2(5H)-ones

Abstract

3,4-Disubstituted furan-2(5H)-one fragment is present in many natural biologically active compounds. In particular, furan-2(5H)-one derivatives containing nonidentical aromatic substituents in positions 3 and 4 of the furan ring exhibit various biological activities [1]. An example is the anti-inflammatory drug Rofecoxib [4-(4-methanesulfonylphenyl)-3-phenylfuran-2(5H)-one]. Eutypoid A isolated from the marine mangrove fungus Eutypa sp. (# 424) [2] and gymnoascolides [3] isolated from the Australian soil ascomycetes Gimnoascus reessii and Malbranchea filamentosa IFM41300 are naturally occurring 3,4-disubstituted furan-2(5H)-ones. We have previously [4–8] synthesized unsaturated γ-lactones bearing heteroaromatic substituents in the 3-position of the lactone ring and revealed biological activity of benzimidazolyl-, benzothiazolyl-, and benzoxazolyl-substituted furan-2-ones. In the present article we report the synthesis of dihydrofuranones containing a 5-amino-4,6-dicyanobiphenyl-3-yl substituent on C. Cyclocondensation of α-hydroxy ketones 1–4 with ethyl acetoacetate in the presence of sodium ethoxide [9–11] gave the corresponding 4,5,5-trisubstituted 3-acetylfuran-2(5H)-ones 5–8 which reacted with malononitrile according to Knoevenagel (by heating in boiling benzene in the