Unfolded and macrocyclic ammonium derivatives of diterpenoids steviol and isosteviol having choline moieties. Synthesis and inhibitory activities toward acetylcholine- and butyrylcholinesterases

A series of unfolded and macrocyclic ammonium derivatives of diterpenoids isosteviol 2 and steviol 17 possessing choline moieties have been synthesized and assayed for inhibitory activities toward AchE and BchE. Compounds 5–8 , 13 , 16 , 20 , and 21 showed moderate activity within the range of IC 50 values 8.0 × 10 −4 to 2.2 × 10 −6 mol L −1 . Isosteviol derivative 16 exhibited the best inhibition selectivity against acetylcholinesterase among the compounds tested. It inhibited AchE of human erythrocytes at IC 50 = 80 μM, whereas inhibition of BchE occurred at IC 50 > 1000 μM.