Efficient synthesis of substituted 7-methyl-2H,5H-pyrano[4,3b]pyran-5-ones and evaluation of their in vitro antiproliferative/cytotoxic activities

Substituted 7-methyl-2H,5H-pyrano[4,3-b]pyran-5-ones and related heterocycles 3 were synthesized through an efficient domino Knoevenagel condensation/6 pi-electron electrocyclization. In vitro antiproliferative/cytotoxic activity evaluation was performed with human SH-SY5Y neuroblastoma cells and revealed IC50 values ranging from 6.7 to > 200 mu M. The compound that was most cytotoxic to the neuroblastoma cells, that is, 2-isobutyl-3-isopropyl-7-methyl-2H,5H-pyrano[4,3-b]pyran-5-one (3a), also exhibited necrotic effects on the human IPC melanoma cells. (c) 2006 Elsevier Ltd. All rights reserved.