Abstract
ACETYLCHOLINE, (CH3)3N+CH2CH2OCOCH3, the transmitter substance in cholinergic nervous systems, is a flexible molecule and the structure of active rigid analogues is therefore valuable for the determination of the conformation relevant to the various cholinergic systems. The muscarinic and nicotinic activities and the rate of hydrolysis by acetylcholinesterase of the isomers and enantiomers of 2-acetoxy cyclopropyl trimethylammonium iodide (ACTM) have been extensively studied by Long, Cannon, Armstrong and Chiu1,2. Their investigation was part of an attempt to determine the value of the transoid cisoid theory3 of the conformations of cholinergic molecules at muscarinic and nicotinic receptors respectively, using relatively rigid analogues of acetylcholine. The racemic compound (+,−)-cis-ACTM was shown to be relatively inactive in all cholinergic systems. The (+)-trans-enantiomer of ACTM was shown to be more potent than the (−)-trans-enantiomer in all cholinergic receptor systems and to be more rapidly hydrolysed by acetylcholinesterase as shown in Table 1. We have analysed the crystal structure of (+)-trans-ACTM by means of X-ray diffraction and determined the absolute configuration of the molecule by use of the effect of anomalous dispersion.
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CHOTHIA, C., PAULING, P. Biological Sciences: Absolute Configuration of Cholinergic Molecules; the Crystal Structure of (+)-trans-2-Acetoxy Cyclopropyl Trimethylammonium Iodide. Nature 226, 541–542 (1970). https://doi.org/10.1038/226541a0
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DOI: https://doi.org/10.1038/226541a0
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