Synthesis and Characterization of the Enantiomerically Pure cis ‐ and trans ‐2,4‐Dioxa‐3‐fluoro‐3‐phosphadecalins as Inhibitors of Acetylcholinesterase

The title compounds, the P(3) ‐axially‐ and P(3)‐ equatorially‐substituted cis ‐ and trans ‐configured 3‐fluoro‐2,4‐dioxa‐3‐phosphadecalin 3‐oxides (=3‐fluoro‐2,4‐dioxa‐3‐phosphabicyclo[4.4.0]decane 3‐oxides) have been prepared (ee>99%) and fully characterized. The compounds are irreversible inhibitors of acetylcholinesterase, and both the kinetic data and the mechanisms of the inhibition are determined by a novel enzyme‐kinetic approach that is described in the preceding report. The inhibitors display pronounced stereoselectivity, and several of them are significantly stronger than diisopropyl fluorophosphate that is generally used as a potent standard.