Total Synthesis of (-)-Aristoquinoline via an Intramolecular Nitrilium Ion Cyclization

The enantioselective total synthesis of the alkaloid aristoquinoline has been achieved in seven steps and 26% overall yield. A new preparation of the useful synthetic building block (-)-alpha-terpinyl amine was also developed in order to avoid stoichiometric mercury reagents or azide-containing intermediates. Key steps in the optimized synthetic route include an intramolecular nitrilium ion cyclization to form the characteristic azabicyclo[3.3.1]nonane ring system and a diastereoselective reduction of the resulting imine mixture to afford the natural product. An isomer of aristoquinoline containing an exocyclic alkene was also obtained and found to exhibit unusual chromatographic and spectroscopic properties.

Automated summary

The enantioselective total synthesis of the alkaloid aristoquinoline has been achieved in seven steps with an overall yield of 26%. A new preparation method of the synthetic building block (-)-alpha-terpinyl amine was developed. Key steps in the optimized synthetic route include an intramolecular nitrilium ion cyclization and a diastereoselective reduction of the resulting imine mixture. An isomer of aristoquinoline containing an exocyclic alkene was also obtained with unusual chromatographic and spectroscopic properties.