Asymmetric synthesis of (+)-pilosinine: a formal synthesis of (+)-pilocarpine

✍ Scribed by Gideon Shapiro; Cai Chengzhi

• Publisher: Elsevier Science
• Year: 1992
• Tongue: French
• Weight: 274 KB
• Volume: 33
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)92211-1

✦ Synopsis

An efficient asymmetric synthesis of enantiomerically pure (+)_pilosinine 4 has been achieved in 6 steps from a known chiral bromoacyloxaxolidinone. The imidaxole alkaloid (+)-pilocarpine 1 and analogs have been the subject of considerable study of late due to their therapeutic potential as muscarinic agonists for the symptomatic treatment of Alxheimer's Disease.' The thiolactone 22 and oxaxolidiuone 33 are particularly interesting pilocarpine isosteres. 1 2 3 4

Several racemic syntheses4 and two asymmetric syntheses+ using chiral start@ materials (L-histidine, D-2-aminobutyric acid) of pilocarpiue have been reported. The first reported asymmetric synthesis5" gave a low optical yield and the later synthesisst' is somewhat tedious. We were interested in a practical asymmetric synthesis of natural (+)-pilocarpine and focus& on C4 as the important chiral center