Description
Muscarine is a natural alkaloid that is found in a number of wild mushrooms. Despite the
fact that muscarine does not have any therapeutic value, it is of interest because of its
expressed toxic properties, which made it one of the first systematically studied cholinomimetic substances. This compound was an underlying classification of cholinergic
muscarinic receptors. The action of muscarine is similar to that of acetylcholine on peripheral autonomic effector organs, and atropine is an antagonist to it. Unlike acetylcholine,
muscarine does not act on nicotinic receptors.
Synthesis
Muscarine, 2-methyl-3-hydroxy-5-(N,N,N-trimethylammonium) methylentetrahydrofuran chloride (13.1.14), was first isolated from the poisonous mushrooms
Amanita muscaria. It can be synthesized in various ways from completely different substances [16¨C24], particularly from 2,5-dimethyl-3-carboxymethylflurane, which undergoes a Curtius reaction, i.e. successive reactions with hydrazine and further with nitrous
acid in isopropyl alcohol, which forms the urethane (13.1.9), the acidic hydrolysis of
which gives 2,5-dimethyl-2H-furane-3 (13.1.10). Allylic bromination of this gives 2-
methyl-5-bromomethyl-2H-furanone-3 (13.1.11), which is reacted with dimethylamine,
forming 2-methyl-5-dimethylaminomethyl-2H-fluranone-3 (13.1.12). Reducing this compound leads to formation of 2-methyl-3-hydroxy-5-dimethylaminomethyltetrahydroflurane (13.1.13), the reaction of which with methyl chloride gives muscarine (13.1.14) as a
mixture of stereoisomers.
