Synthesis and anticholinesterase activity of some benzo-1,3,2-dioxaphospholene, oxazaphospholine and diazaphospholine 2-ones containing 2-amino acid substitution

Synthesis of the titled compounds has been described. H-1 NMR, IR band freq uencies and MS fragmentation and rearrangement peaks were analyzed and disc ussed in detail. Studying the inhibitory effect of these compounds on acety lcholinesterase (AChE) showed that dioxaphospholenes were stronger inhibito rs than oxazaphospholines and diazaphospholines. This was explained by incr easing the number of nitrogen atoms around the phosphorus atom in the later two series, which reduces the electrophilic character of the phosphorus at om by the overlapping between the d pi - p pi orbitals of the phosphorus an d the neighboring nitrogen atoms, and hence reducing the electrophilic atta ck of the phosphorus atom on a nucleophilic center at the esteratic site of the enzyme. Steric factor of the amino acid moiety showed stronger effect than the electronic factor on the inhibition activity, the observed order w as glycine > glutamic > methaionine > phenylalanine > alanine.