A New Chromone and Flavone Synthesis and Its Utilization for the Sythesis of Potentially Antitumorigenic Polycyclic Chromones and Flavones

Article abstract of DOI:10.1021/jo00312a023

A new synthesis of chromones and flavones based on the ortho-directed metalation of methoxymethyl aryl ethers with alkyllithium reagents is described.It entails reaction of the ortho-lithiated intermediates with a conjugated unsaturated aldehyde followed by oxidation of the allylic alcohol product with "periodinane" to yield an ortho-allylic ketone.The latter on heating in acetic acid undergoes loss of the methoxymethyl protecting group and cyclization to a chromanone (or flavanone, if a β-phenyl substituent is present).Dehydrogenation by treatment with pyrrolidinehydrotribromide (PHT) in dimethyl sulfoxide yields the corresponding chromones (or flavones).This synthetic approach appears general in its applicability.It has been applied to the synthesis of a series of polycyclic chromone and flavone compounds containing the naphthalene and pyrene ring systems that hold promise as agents for the chemoprevention of cancer.