Scholarship of Discovery
Conformational rigidity has been conferred upon the OCCN portion of acetylcholine by incorporation of the C atoms into a cyclopropane ring. trans-2-Acetoxycyclopropyltrimethylammonium iodide has been prepared from an olefinic starting material, 2-vinyloxytetrahydropyran; assignment of the trans configuration to the 1,2-disubstituted cyclopropane systems was based upon literature precedent and upon nmr data, and was confirmed by X-ray crystallographic analysis. Resolution of one of the racemic intermediates in the reaction sequence was achieved, which permitted preparation of both enantiomers of the final product. X-Ray crystallographic analysis has demonstrated that the muscarinically active (+)-trans-2-acetoxycyclopropyltrimethylammonium iodide possesses the same absolute configuration as the muscarinically active enantiomers of Acetyl-β-methylcholine and muscarine.
Armstrong, P. Douglas and Cannon, Joseph G. . "Small Ring Analogs of Aceylcholine. Synthesis and Absolute Configurations of Cyclopropane Derivatives." Journal of Medicinal Chemistry 13.6 (1970): 1037-1039.