Functionalized CARB Pharmacophore (FCP) approach to thio and unsaturated carbohydrate scaffolds with potential anticancer activity

This brief review discusses some new developments in the functionalized carb pharmacophore (FCP) concept introduced by us in 2014. While the examples concentrate mainly on biological data of selected newly designed carbohydrate molecules, the chemical syntheses are also included. This review also summarizes new developments in the stereoselective synthesis of 1,4-S-thiodisaccharides and 4-S-thiosaccharides, from levoglucosenone (LG) and a preliminary evaluation of their biological activity. New methodologies utilizing a saturated analog of levoglucosenone, dihydrolevoglucosenone (DHLG), in the synthesis of derivative enones bearing heterocyclic and aromatic moieties at the exocyclic position are also discussed. All exocyclic enones were prepared in good yields by straightforward direct aldol condensation of heterocyclic and aromatic aldehydes with dihydrolevoglucosenone under base conditions. When o-hydroxybenzaldehydes were used as substrates, the original condensation was followed by cyclization forming the domino product, a carbohydrate-fused chromanone system. Additionally, when o-hydroxyacetophenones were used, the base catalysed condensation furnished spiro-chromanones in excellent yield. The stereoselectivities of all reactions are discussed and plausible reaction mechanisms are proposed for the formation of chromanone and spiro-chromanone.