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

Abstract

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 diiodide 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.

Sensing Magnetic Field and Intermolecular Interactions in Diamagnetic Solution Using Residual Dipolar Couplings of Zephycandidine

“…The 1 H NMR spectrum of zephycandidine dissolved in methanol- d 4 recorded at 16.445 T (700 MHz spectrometer) is shown in Figure 1 . The assignment of all resonances to the molecular structure agrees fully with previously published data [ 22 , 23 , 24 ].…”

Ru(II)-Catalyzed C–H Functionalization of 2-Arylbenzimidazoles with Iodonium Ylides: A Straightforward Access to Bridgehead Polycyclic N-Heterocycles

“…Considering the significant importance of the imidazole units, , we next explored the scope of the reaction with respect to 2-arylimidazoles (Table ). The reaction smoothly proceeded with neutral and electron-donating substituents on the arene group and provided good yields ( 6a – 6c , 71–79%).…”

“…Bridgehead N -fused [5,6]-bicyclic heterocycles are ubiquitously found in many important drug leads, materials, and natural products . Thus, the synthesis of N -fused [5,6]-bicyclic heterocycles has attracted widespread interest.…”

Tandem Palladium/Copper-Catalyzed Decarboxylative Approach to Benzoimidazo- and Imidazophenanthridine Skeletons

“…Several (dihydro)­imidazophenanthridine derivatives were identified as potent DNA-binding agents with anticancer activities . A naturally occurring alkaloid featuring an imidazophenanthridine core, namely, zephycandidine A, displayed considerable antitumor and antiacetylcholinesterase activities, prompting the synthesis and biological studies of a range of related compounds . Furthermore, several (benzo)­imidazophenanthridines with extended π-systems have been applied as components of organic light-emitting diodes (OLEDs), while (dihydro)­imidazophenanthridinium salts of polyoxometalates (POMs) were found to undergo highly unusual spontaneous self-assembly into microtubular structures …”