Abstract

A short and efficient synthesis of (+)-pilocarpine (1) has been accomplished in 10 steps and 51% overall yield from L-aspartic acid. The synthesis features a diastereoselective alkylation of a protected aspartic acid diester derivative and a selective hydrolysis of the α-methyl ester to give the corresponding amino acid. Subsequent replacement of the amino group with bromo, esterification, and a modified Reformatsky reaction with 1-methylimidazole-5-carboxaldehyde (8) afforded imidazole-substituted lactone 28

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