Efficient and stereoselective synthesis of sugar fused pyrano[3,2-c]pyranones as anticancer agents

Abstract

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2-c]pyranone derivatives starting from inexpensive, naturally occurring D-galactose and D-glucose. First, β-C-glycopyranosyl aldehydes were synthesized from these D-hexose sugars in six steps, with overall yields 41–55%. Next, two different 1-C-formyl glycals were synthesized from these β-C-glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1-C-formyl galactal and 4-hydroxycoumarin. Next, 1-C-formyl galactal and 1-C-formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1–2 h in the presence of L-proline to obtain exclusively single diastereomers of pyrano[3,2-c]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds.