Synthetic Study Towards The Daphniphyllum Alkaloids Daphnicyclidin A

In this thesis,the synthesis and related explorations of the ACD tricyclic core skeleton(7/5/7 ring system)of natural product Daphnicyclidin A type Daphniphyllum alkaloids was explored.Daphniphyllum alkaloids are a class of triterpenoid alkaloids with unique and novel structure and certain biological activity.So far,more than 320 alkaloids have been isolated and identified from the Daphniphyllum genus,and they are divided into 14 categories based on their skeletal structure characteristics.Daphnicyclidin A type alkaloids has been isolated and identified by Prof.Kobayashi since 2001.It has a highly fused 7/6/5/7/5/6 six-ring system and five chiral centers,one of which is a full-carbon quarter carbon center(C5).At the same time,Daphnicyclidin A contains two seven-membered parallel ring fragments(rings A and D)with large ring tension and rare cyclopentadiene structural fragment(ring E)in natural products.It has been separated for 19 years,but there is still no report on the total synthesis of this type of alkaloidsIn this study,the Type I [5+2] cycloaddition reaction developed by our group was used as the key strategy.After carrying out the retrosynthetic analysis,a commercially available compound cyclopentenone was proposed as the starting material.The Rubottom oxidation,1,3 carbonyl migration,and triflate esterification was used to modify the ring A.The furan structural fragments were then coupled by a Mitsunobu reaction.After removing the silyl group,the Achmatowicz reaction was used to oxidize and rearrange furan to obtain a pyranone compound,which is the [5+2] reaction precursor.After several attempts,an intramolecular [5+2] cycloaddition reaction was achieved under acid-catalyzed conditions to construct the ACD tricyclic core structure of Daphnicyclidin A.By analyzing the single crystal data,it was determined that its relative configuration was consistent with the target molecule.Finally,in this study,the key reaction was optimized by modifying the furan structural fragment to increase the yield of the Type I [5+2] cycloaddition to 62%.So far,this thesis has completed the construction of the Daphnicyclidin A tricyclic core skeleton,laying the foundation for subsequent total synthesis work.At the same time,it proved that the [5+2] cycloaddition reaction was efficient and concise in constructing the middle ring system.