Asymmetric Synthetic Studies Of Indole Alkaloids Arborisidine,Koumine And Strictamine

This thesis aims at collective total synthesis of several structurally related monoterpenoid indole alkaloids and focuses on asymmetric synthetic studies of Kopsia alkaloid arborisidine,Gelsemium elegans alkaloid koumine and akuammiline alkaloid strictamine.This work mainly consists of the following two parts.In the first part,the asymmetric synthetic studies of indole alkaloid arborisidine and koumine were conducted by using the common tetracyclic intermediate 2-31,which was employed in the formal synthesis of strictamine in early;in the second part,the first generation total synthesis of strictamine was accomplished on the basis of common tetracyclic intermediate 2-31 and the second generation synthetic study of akuammiline alkaloid strictamine was developed by using photo-catalyzed radical cascade cyclization methodology reported by our group.Part one describes the asymmetric synthetic studies of monoterpenoid indole alkaloid arborisidine and koumine.We completed the synthesis of tetracyclic intermediate 2-31 in an optically pure by using L-tryptophan as starting material through Pd-catalyzed alkylation,NBS/PPTS mediated electrophilic cyclization and copper-catalyzed Friedel-Crafts cyclization.With the discovery of reductive ring-openging reaction induced by TiCl₄/NaBH₃CN,compound 2-31 act as pyrroloindoline derivative can be used in the asymmetric synthetic study of monoterpenoid indole alkaloids.The asymmetric synthetic study of alkaloid arborisidine was started from the common tetracyclic intermediate 2-31 and critical transformations including Karpcho decarboxylation,reductive ring-opening,Saegusa oxidation and aza-Michael addition were adopted to build the D-ring and C16 nitrogen-containing quaternary center.However,when we sought to construct the final E-ring,all ring-closing strategies were failed due to a retro-Michael process of the key substrate,which lead to disruption of the research.In the asymmetric synthetic study of monoterpenoid indole alkaloid koumine and this work began with the common tetracyclic intermediate 2-31.The C20quaternary center was constructed by Claisen rearrangement.A reductive ring-opening of the pyrrole moiety was accomplished by treatment with TiCl₄/NaBH₃CN and the piperidine F-ring was synthesized through lactamization.Unfortunately,when we attempted to flip the C5 chiral center,oxidation of primary alcohol easily produced alkenal,which can not be used in the subsequent step.Further attempts to furnish selective 1,4 reduction or olefination of alkenal was proven to be impossible.Part two discloses the asymmetric synthetic study of monoterpenoid indole alkaloid strictamine.In order to solve the challange encountered by most synthetic chemists on building the C15-C20 bond in piperidine E-ring of strictamine,we designed the first generation synthetic strategy,conquered this problem by rearrangement to construct C15-C20 bond and completed the preparation of E-ring via final alkylation at N4.But some key transformations were inefficient,such as the poor diastereoselectivities in Johnson-Claisen rearrangement.On the purpose of solve the above scientific problems betterly and expand the application scope of the new high efficiency photo-catalyzed radical cascade cyclization methodology developed by our group,the second generation synthetic study of strictamine was proposed base on the nitrogen-containing heterocyclic intermediate,which was obtained from the radical cascade cyclization.A Tsuji-Trost allylation was adopted to construct the D-ring and C7quaternary center.A Pd₂?dba?₃-catalyzed reductive Heck coupling reaction was applied to build the E-ring and construct the key framework.The reaction yielded the advanced intermediate with a 2.5:1 ratio of diastereoselectivity,in which the C16 configuration in major isomer was contrary to what we expected.We intend to adjust the strategy for build E-ring in the near future.