Racemic N'-norphenserine and its enantiomers:unpredicted inhibition of human acetyl-and precursor protein in vitro

摘要

The optically pure enantiomers of N'-norphenserine (15,16) were synthesized and its racemate 17 was prepared by mixing equal parts of each enantiomer.(-)-N'-Norphenserine (15) was prepared by partial synthesis initiated from the natural product,(-)-physostigmine (1).(+)-N'-Norphenserine (16) was prepared by total synthesis using the Julian oxindole route,with modifications.The in vitro inhibitory activities of 15-17 were quantified against human erythrocyte AChE and plasma BChE as well as against human neuroblastoma cell beta-amyloid precursor protein secretion in cell culture.All were active.Racemic compound (17) with a high AChE and beta-amyloid precursor protein inhibitory action may warrant further assessment in Alzheimer's disease models.