Total Syntheses of the Imidazo[1,2‐f]phenanthridine‐Containing Alkaloid Zephycandidine A

Two distinct and concise syntheses of zephycandidine A (1) from readily available starting materials are reported. In the first, the imidazole derived from piperonal (7 a) was subjected to reaction with o‐bromoiodobenzene or the corresponding di‐iodide in the presence of Pd[0] and thereby forming, via Buchwald–Hartwig and Heck reactions, a mixture of target 1 and regio‐isomer 10. These products could only be separated from one another by HPLC. A lower yielding but completely regioselective synthesis of zephycandidine A (1) was achieved by palladium‐catalyzed cross‐coupling of the imidazole, 6 b, derived from the bromopiperonal 7 b with o‐iodophenylboronic acid (5 d). Preliminary biological screening of compounds 1, 10 and certain precursors reveal that some possess anti‐viral properties but, contrary to expectations, are not notable inhibitors of acetylcholinesterase.