Biomimetic Synthesis of (+-)-Galanthamine and Asymmetric Synthesis of (-)-Galanthamine Using Remote Asymmetric Induction

摘要

(+-)-Galanthamine (1) was synthesized in excellent yield by applying PIFA-mediated oxidative phenol cou- pling of N-(4-hydroxy)phenethyl-N-(3',4',5'-trialkoxy)benzyl formamide (15b) as a key step.Because of the sym- metrical characteristics of the pyrogallol moiety in the substrate (15b),the phenol coupling resulted in a sole cou- pling product except for volatile components from the oxidizing agent.On the basis of the successful results of the above strategy,(-)-galanthamine (1) was synthesized by employing a novel remote asymmetric induction, where conformation of the seven-membered ring in the product of the phenol coupling was restricted by forming a fused-chiral imidazolidinone ring with D-phenylalanine on the benzylic C-N bond of the tri-O-alkylated gallyl amino moiety.The conformational restriction and successive debenzylation of the protected hydroxyl groups on the pyrogallol ring caused diastereoselective cyclization to yield a cyclic ether having the desired stereochemistry for the synthesis of (-)-l.