120230-65-1Relevant academic research and scientific papers
An Effective Chirospecific Synthesis of (+)-Pilocarpine from L-Aspartic Acid
Dener, Jeffrey M.,Zhang, Lin-Hua,Rapoport, Henry
, p. 1159 - 1166 (2007/10/02)
A short and efficient synthesis of (+)-pilocarpine (1) has been accomplished in 10 steps and 51percent 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.Details concerning this novel lactone synthesis are also described.Finally, hydrogenolysis of the lactone carbon-oxygen bond and selective reduction of the resulting monoester afforded pure (+)-pilocarpine (1).
