Total Synthesis of the Major Metabolite of Methoxsalen

Article abstract of DOI:10.1021/jo01296a024

The total synthesis of the 6-coumarinylacetic acid (15), the major metabolic isolate of methoxsalen (1), starting from umbelliferone (5) is described.Several derivatives of a second metabolite, 4, were also prepared from the common intermediate aldehyde 13.This preparation involves a novel rearrangement of the bromoacetate 20 to the acetoxyphenol 21.A mechanism for the displacement reactions of the metabolite 4 and its derivative 21 implicating the transient enone 24 is presented.