An improved synthesis of the enantiomers of bm‐5 and their effects on the central in vivo release of acetylcholine

Racemic N ‐methyl‐ N ‐(1‐methyl‐4‐pyrrolidino‐2‐butynyl)acetamide (BM‐5), a putative postsynaptic agonist and presynaptic antagonist at muscarinic receptors, was resolved into the enantiomers by a new method suitable for large scale preparation. The method involves a chemoselective N ‐debenzylation as the key step. The enantiomers of BM‐5 were obtained after six separate steps in 25% overall yield. The ability of the enantiomers to release acetylcholine was evaluated in vivo by use of brain dialysis. (R)‐BM‐5 was the more potent enantiomer in this assay. © 1992 Wiley‐Liss, Inc.