Study On The Synthesis And Structural Modification Of PPAPs Without Side Chains At The 5-position

Objective : Total syntheses of a series of 5-unsubstituted PPAPs,Oblongifolin M(OM),and relevant natural products,oblongiforin L(OL),oblongiforins P(OP),oblongiforin AA(OAA)and garciniaphenone,with similar structure,So that to solve the problem of limited amount of such active natural products.Methods and Results: In chapter ?,the total syntheses of natural PPAPs were summarized,and a new methodology for the syntheses of bicyclo[3.3.1]nonane-2,4,9-triketone skeleton was proposed after studying the structural properties of the natural PPAPs in depth: Bicyclic[3.3.1]nonane-2,4,9-triketone can be obtained from chain substrates by two cascade Dieckmann condensation reactions,and then the total syntheses of natural products can be accomplished.In chapter ?,model reaction is designed to prove the feasibility of the new methodology.We prepared four chain substrates,in two different types,and screened a great deal of conditions.Finally,a six-membered and an eight-membered ring products with cyano group were obtained.It was found that the two products originated from the target molecule,bicyclic[3.3.1]nonane-2,4,9-triketone products,by theoretical deduction and NMR analysis.Therefore,the feasibility of the new methodology was proved.In chapter ?,on the basis of model reactions,the total synthesis of target natural products was started.The corresponding chain substrates were obtained by employing different alkylation reagents(Me I,prenyl bromide,geranyl bromide)during the alkylation reactions,and then a series of 5-unsubstituted bicyclic[3.3.1]nonane-2,4,9-triketone cores with different side chains on C-7 were accomplished via two cascade Dieckmann condensations.Finally the first total synthesis of OL,OP,OAA and garciniaphenone were accomplished by C-3 acylation using benzoyl cyanide.OM was obtained from OL via Baeyer-Villiger oxidation.All target compounds could be obtained over 1 g scale,which solved the scarcity of this active natural products.During the synthesis process,we found the C-7 absolute configuration of OL,OP,OAA and OM were problematic,so the C-7 absolute configuration of these compounds were revised.Cis and trans PPAPs can be obtained simultaneously via our synthetic approach.Conditional screening showed that C-7 side chains could control the configuration of C-1 and C-5 chiral centers during the construction of bicyclic[3.3.1]nonane-2,4,9-triketones skeleton,and cis or trans bicyclic[3.3.1]nonane-2,4,9-triketones skeleton can be obtained selectively.Control experiments indicated that the cascade Dieckmann condensation processed via a eightmembered intermediate.Conclusions: A new methodology for constructing bicyclic[3.3.1]nonane-2,4,9-triketone skeleton of natural PPAPs has been developed,and the total synthesis of five natural products has been accomplished.During the synthesis process,the C-7 absolute configuration of OL,OP,OAA and OM were found to be problematic,so we revised their structures.The gram-scale synthesis of all target natural products can be achieved convenient,which can solve the scarcity of this active natural products.