Studies On The Asymmetric Total Synthesis Of Versiquinazoline H And Preliminary Studies On The Aza-Robinson Reaction

Alkaloids distribute widely in nature and have many pharmacological activities.Many alkaloids have been applied in traditional or modem medicine,but alkaloids that can be directly used by human beings are still very limited in nature.Therefore,the preparation of natural products through green and efficient synthesis methods is an effective way to solve the problem.(-)-Verslquinazoline H is a new fumiquinazoline-type alkaloid that has been isolated from the gorgonian-derived ftmgus Aspergillus versicolor LZD-14-1.There hasn,t been reported about its total synthesis.Bicyclic vinylogous lactams are key structures of many medicinal agents and are often used as synthetic intermediates in the preparation of many alkaloids.This paper maiily includes the following two parts:(1)the total synthesis of versiquinazoline H;(2)exploration of aza-robinson cyclization reaction based on amide activation.Through the work of this thesis,we have obtained the following results:1.By employing our previously developed strategy,we have completed the first total synthesis of both the proposed and the revised structures of versiquinazoline H and its diastereoisomer.Modify the last lactamization step,and devoted it to the synthesis of(-)-isochaetominine A and 11-epi-isochaetominine C and improved the yield respectively.2.By simply altermating the quenching conditions for the key DMDO-triggered double cyclization,we achieved:(1)a five-step diastereodivergent total synthesis of three diastereomers of versiquinazoline H;(2)a diastereoconvergent synthesis of two diastereomers of versiquinazoline H and confirmed their absolute configuration by X-ray;(3)the enantiodivergent syntheses of(+)-and(-)-14-epi-isochaetominine C,as well as(-)-and(+)-11-epi-chaetominine.3.Isolated and confirmed two diastereomeric:1,3-dioxolanes as intermediates of the DMDO oxidation for the first time,and transformed it into the momo-/double cyclization product respectively,which allowed suggesting a plausible mechanism for the DMDO-triggered double cyelization reactions.4.We hoped to develop a strategy to synthesis bicyclic vinylogous lactams through Michael addition reaction,the preparation of silyl enol ether and the activation of amide in three steps.We have successfully explored the optimal conditions for the Michael addition reaction in the first step.For the second step,if the starting material has no substituent at internal ortho position of ketone group,two kinds of silyl enol ether in bad ratio will be generated with a low yield.If there is a methyl at the same position,we can produce dynamic silyl enol ether at a yield of 85%and a ratio of 100%.Unfortunately,the yield of last step wasn't high,which needs to be further explored.(?)...