Electrochemical oxidation of aspidofractinine-type alkaloids: Formation of kopsine, kopsidine, kopsinitarine and bisindole derivatives

Anodic oxidation of kopsamine on platinum in acetonitrile results in cyanation or cyanomethylation, following ring closure, while oxidation on vitreous carbon in methanol yields a dimerization product with a C-2 element of symmetry. This behaviour is reproduced in the aromatic congeners of kopsamine, kopsiflorine and 11-methoxykopsilongine. Oxidation of kopsingine on platinum in CH2Cl2-MeCN leads to a stable conjugated iminium salt which can be trapped by alcohol or water nucleophiles to give kopsidines A, B, and C. Kopsidines A and B can also be obtained directly from electrooxidation in methanol or ethanol. Oxidation of dihydrokopsingine in acetonitrile gives the 17-to-5 and 17-to-3 oxo-bridged compounds directly, while oxidation in methanol yields an additional product which is a caged kopsinitarine derivative. Oxidation of an aspidofractinine derivative without unsaturation in the piperidine ring and with a C(17)-alpha OH function gives a C-2 symmetric dimerization product as well as a caged kopsinitarine-type product. Possible pathways leading to the various products are presented.