Asymmetric Total Synthesis Study Of (-)-(6S,2'R)-Cryptocaryalactone And 2-substituted Piperidine Alkaloids

Substituted?,?-unsaturated?-lactones,as well as 2-substituted piperidine alkaloids are an important two class of natural products with a wide range of biological activity.?-?-?6S,2'R?-Cryptocaryalactone was isolated from Cryptocarya moschata by Spencer and coworkers in 1984.It has been shown to possess the biological activity of inhibiting the seed germination that may be related to the unsaturated moiety due to its potential to act as a Michael acceptor.2-Substituted piperidine alkaloids mainly isolated from the genus sedum contain a stereogenic piperidine ring unit,which display a memory-enhancing properties and also are used in the treatment of cognitive disorder.In this thesis,we designed a novel,diversity strategy for the stereoselective total syntheses of?-?-?6S,2'R?-Cryptocaryalactone and2-substituted piperidine alkaloids.In this strategy,we first installed the chiral hydroxyl using Evans aldol reaction.Then,in the presence of Ti?O-i-Pr?₂Cl₂,anti-1,3-diol was selectively constructed via the alkoxy-directed Mukaiyama aldol reaction.With this anti-1,3-diol in hand,we could accomplish the total synthesis of?-?-?6S,2'R?-Cryptocaryalactone via few steps including construction the?,?-unsaturated?-lactone through Yamaguchi lactonization and conversion of the hydroxyl protection group.Also,we could obtain?-?-Allosedridine,?+?-Sedridine,?-?-Coniine,?+?-Pelletierine,?-?-Sedamine and?-?-Allosedamine through azide formation,reduction and so on.Inthisthesis,wedesignedaunifiedsyntheticrouteof?-?-?6S,2'R?-Cryptocaryalactone and 2-substituted piperidine alkaloids.This approach was simple,feasible,efficient and highly selective,which has important implications for the asymmetric total synthesis of other natural products containing?,?-unsaturated?-lactone unit and 2-substituted piperidine alkaloids.