ENANTIOENRICHED N-(2-CHLOROALKYL)-3-ACETOXYPIPERIDINES AS POTENTIAL CHOLINOTOXIC AGENTS - SYNTHESIS AND PRELIMINARY EVIDENCE FOR SPIROCYCLIC AZIRIDINIUM FORMATION

The syntheses of six enantioenriched analogs representing cyclic forms of acetylcholine are reported. (S)- and (R)-N-(2-chloroethyl)-3-aceto xypiperidine and (R,R)-, (R,S)-, (S,R)-, and (S,S)-N-(2-chloropropyl)- 3-acetoxypiperidine have been synthesized from (R)- or (S)-3-hydroxypi peridine in five steps. (R)- and (S)-3-hydroxypiperidine were accessed via parallel stereospecific routes from d- and 1-glutamic acid, and t hrough fractional recrystallization of diastereomeric tartranilic acid salts. (S)-N-(2-Chloroethyl)-3-acetoxypiperidine was reacted with sil ver perchlorate to form a spirocyclic aziridinium analog of acetylchol ine as evidenced by a characteristic H-1 NMR shift for the aziridinium methylene groups.