Cryptocaryols A−H, α-Pyrone-Containing 1,3-Polyols from Cryptocarya sp. Implicated in Stabilizing the Tumor Suppressor Pdcd4

Abstract

A high-throughput cell-based reporter assay designed to identify smallmolecule stabilizers of the tumor suppressor Pdcd4 was used to screen extracts in the NCI Natural Products Repository. Bioassay-guided fractionation of an extract from a Papua New Guinea collection of the tropical tree Cryptocarya sp. provided a series of new 5,6-dihydro-alpha-pyrone-containing 1,3-polyols (1-8), named cryptocaryols A-H. Their structures were assigned from a combination of NMR, MS, and CD studies in conjunction with NMR database comparisons. Compounds 1-8 were found to rescue Pdcd4 from TPA-induced degradation with EC50 concentrations that ranged from 1.3 to 4.9 μM.