NMR determination of pKa values of indoloquinoline alkaloids.

Malaria is one of the most serious global health problems. Isolating new therapeutic agents with potential antimalarial activity from natural sources or preparing such agents either semisynthetically or synthetically is one strategy for solving the problem of resistance constantly evolving to the drugs currently in use. For alkaloids, the acid-base dissociation constant, pK(a), is an important characteristic, thought to be associated with biological activity. In this contribution, pK(a) values for several indoloquinoline alkaloids were determined by using (1)H NMR spectroscopy in a mixture of solvents. The data were recalculated for water solutions using the correction factors reported previously. The structural dependence of the pK(a) values for cryptolepine and its isomers neocryptolepine, isocryptolepine and isoneocryptolepine as well as some substituted neocryptolepine derivatives is discussed. 2009 John Wiley & Sons, Ltd.