A Convenient Synthesis of <scp>L</scp>(+)-Muscarine

Abstract

A new total synthesis of L(+)-muscarine is described. Performic acid oxidation of N-acetylcrotylglycine gave the corresponding 4,5-diol which was resolved at the α-carbon by stereospecific hydrolysis of the N-acetyl group of the L-isomer with hog kidney acylase I. The resulting α-L(+)-aminoacid diol (3; Chart 1) was deaminated with nitrous acid to give 4-hydroxy-5-methyl-2-tetrahydrofuran carboxylic acid with retention of configuration at position 2. Reaction of the corresponding methyl ester with dimethylamine gave two major amide constituents in 65% yield. Reduction of these two N,N-dimethylamides (5a and b) with lithium aluminum hydride followed by quaternization with methyl iodide afforded a pure isomer of L(+)-muscarine (6a) and L(+)-muscarine (6b) in high yields. The biological activity of the latter was the same as that of the natural alkaloid.