Azapsoralens. Synthesis of 8-Azapsoralens

Article abstract of DOI:10.1021/jo00290a019

The synthesis of some N-methyl-8-azapsoralen salts 1 is described for use as water-soluble analogues of psoralens.A key intermediate is the furopyridine carboxaldehyde 16 prepared in four steps from simple acyclic precursors.The pyrone ring is fused on by first extending the carbon chain via a Reformatsky or Doebner condensation followed by deprotection and ring closure.Since stability of this ring system in water is crucial to its potential use as a nucleic acid cross-linking reagent, rates of pyrone hydrolysis for the N-methylazapsoralens were measured.Sufficient stability in the necessary pH range was found for several analogues.