Synthetic Studies Towards Monoterpene Indole Alkaloid Arboridinine And Cembranoid Natural Products

This dissertation mainly includes the synthetic studies of monoterpene indole alkaloid arboridinine and cembranoid natural products.It is divided into two parts:Part 1:synthetic studies of natural product arboridinine:arboridinine has a unique caged skeleton and contains four chiral centers including two all-carbon quaternary centers and one tertiary alcohol.In recent years,there are many synthetic reports about arboridinine.However,all previous syntheses used stepwise approach to construct the caged pentacyclic system.we intended to investigate the efficient construction of the unique cage-like skeleton of arboridinine through a double-Mannich reaction.Aα-carboethoxylation of the known compound 1-38a/b resulted in multisubstituted compound 2-3.A stereoselective double-Mannich reaction of the complex multisubstituted 2-3 was used to form the caged pentacyclic system,the core structure of arboridinine,under conditions of ammonium acetate and formalin.Then,the exocyclic C14-C15 double bonds could be operated with a typical Peterson olefination process.Under the conditions of Pd/C,HCO₂NH₄,Me OH and Et OAc,the N1-debenzylation was achieved.A concise formal synthesis of arboridinine has been achieved by us.In this part,we realized the efficient synthesis of core structure of arboridinine.Part 2:synthetic studies of cembranoid natural products:cembranoid natural products are widely distributed in nature.More than 300 cembranoid natural products have been isolated up to date and some of them exhibit good antitumor activity.Some cembranoid natural products have a special 14-membered macrocyclic basic skeleton,from which a variety of molecular structures could be formed through different processes.Fragilolide A and scabrolide A,as the representative of highly oxidized cembranoid natural products,have been pursued by synthetic chemists since their isolation.Structurally,fragilolide A bears a sterically compact6/7/5/5 tetracyclic skeleton and eight stereocenters,and six of which are contiguous chiral centers.During the syntheses of cembranoid natural products with 6/7/5/5 tetracyclic skeleton,an Achmatowicz rearrangement reaction of furfuryl alcohol derivative 4-46 gave dihydropyranone derivative 4-47.Then the hydroxyl group of 4-47 was creatively protected by TMS,and then the connection of two fragments between TMS-protected dihydropyranone 4-50 and unsaturatedγ-butyrolactone 4-55 were realize by aldol reaction.The key intramolecular[5+2]cycloaddition reaction involved the oxidopyrylium ylide to form 6/7/5/5tetracyclic skeleton,and the structure of the[5+2]cycloaddition product was confirmed by X-ray crystallography.A series of studies have been carried out on the reductive cleavage of the C7-and C13 oxygen bridge.The reductive cleavage of the C7-O bond was realized by Sm I₂.And the reduction of the hemiketal 4-90 was achieved under the condition of sodium borohydride.The investigation of cleavage of the C13-O bond is still under study.In this part,the 6/7/5/5 tetracyclic skeleton of the cembranoid natural products was formed efficiently by the intramolecular[5+2]cycloaddition reaction.