Acetylcholine (ACh) is the most widely studied of all neurotransmitter substances. For normal nerve function, the enzyme acetylcholinesterase (AChE) must hydrolyze ACh into its basic chemical constituents, choline and acetate. AChE is readily inhibited by organophosphorus (OP) compounds like sarin and soman--both nerve gases--as well as various pesticides. OP compounds also have been widely used to study the mechanism of ACh hydrolysis via AChE. In the 1980s, two studies using OP inhibitors examined the stereoselectivity of AChE hydrolysis. However, they yielded conflicting results. Hence, it is hoped that new studies with a novel OP compound will provide definitive information about the stereoselectivity of the mechanism of AChE action. Obviously, the first phase of this project must be the synthesis of that novel OP inhibitor. We present our efforts in that area and outline future directions.



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