Study On The Synthesis Of The Alkaloid Daphnilactone B

Daphnilactone B is a kind of triterpenoid alkaloid isolated from the fruit of Daphniphyllum oldhami Rosenth in 1974 by Yamamura group.The preliminary bioactivity study of daphnilactone B indicated that it possesses moderate antitumor activity.Many research groups have been attracted to conduct the synthesis of daphnilactone B duo to its dazzlingly three-dimensional structure and potential bioactivity.However,only several methods have been reported toward the construction of its partial ring system,the total synthesis has not been reported so far.In view of this,based on the previous research results of our research group,this paper adopts two different strategies,Dieckmann condensation and intramolecular decarboxylation free radical conjugate addition,to study the synthesis of the core skeleton of daphnilactone B.The achievement of this thesis as follows:(1)Using chiral 4-hydroxyproline methyl ester as raw material,through 10 steps transformation,inculding Dieckmann condensation,Suzuki coupling,catalytic hydrogenation reduction of double bonds,alkylation of ?-position of ester,etc.The key intermediate of 241 was successfully syntheiszed,which contains the AB core and four continuous chiral centers of daphnilactone B.(2)Using 2,3,4-cis-trisubstituted pyrrolidine 203 as raw material,which was prepared in large quantities via the method developed by our research group,the spiro compound 267 was synthesized through 14 steps transformation,including selective protection of hydroxyl group,Boron catalyzed Aldol reaction and ruthenium as photosensitizer catalyzed decarboxylation radical addition reaction,etc.In spite of the desired conjugate addition product 265 was not obtained,the experimental results still enrich the radical chemistry in complex systems and point the way for the design of new substrates.