Synthesis of anti-proliferative [3.3.0]furofuranone derivatives by lactonization and functionalization of C-glycosyl compounds

The [3.3.0]furofuranone structure is found in numerous families of biologically active natural products. We took advantage of the stereodiversity afforded by carbohydrate derivatives to prepare several compounds structurally similar to goniofufurone and crassalactones which are natural cytotoxic agents. We designed and synthesized several stereoisomers of these natural compounds via lactonization of C-glycosyl compounds bearing an hydroxyl on position 4 and a methyl ester on the pseudo-anomeric positionThe reactivity of this bicyclic moiety was explored through etherification of hydroxyls in position 5 and 7 and various substituants (halogen, phenyl, benzyl, cynanmoyl) were introduced. The anti-proliferative properties of these mimics were then evaluated on various cancer cell lines and two compounds 24 and 35 demonstrated IC50 value of 1.34 mu M (U251) and 7.60 mu M (U87) respectively.

Automated summary

The [3.3.0]furofuranone structure is present in various biologically active natural products. Stereodiversity offered by carbohydrate derivatives was utilized to prepare compounds similar to goniofufurone and crassalactones. Several stereoisomers were synthesized via lactonization of C-glycosyl compounds, with some demonstrating significant anti-proliferative properties on cancer cell lines. Two compounds, 24 and 35, showed promising IC50 values on U251 and U87 cell lines.