A furan ring expansion approach to the synthesis of novel pyridazino-psoralen derivatives

A convenient preparation of the parent tetrahydrobenzodifuran was developed from resorcinol. The oxidation of one or both furan rings of this key intermediate was accomplished with DDQ and the resulting benzodifuran was subsequently reacted with 3,6-dimethoxycarbonyl-1,2,4,5-tetrazine to afford the expected pyridazino-psoralen derivative in good yield. This simple method allowed the efficient preparation of a pyridazino-psoralen derivative with a formyl group at C-7, which was introduced by directed ortho-lithiation in the intermediate . An aminoalkyl side-chain was also introduced to the tetracyclic skeleton through the aldehyde functionality in a reductive amination process, which was accompanied by an unprecedented reduction of the pyridazine ring.