InI₃-Catalyzed Polyene Cyclization And Its Application In The Synthesis Of Natural Products And The Total Synthesis Of Miltiorin A

This thesis consists of the following two parts:I.In I₃-catalyzed polyene cyclization of allenes and its application in the total synthesis of seven abietane-type diterpenoids;II.the total synthesis of miltiorin A.In the first part of the thesis,the developed polyene cyclization methodologies are summarized and categorized by initiators,which can be normally classified into the following six categories:cyclization reactions initiated by alkene,alkyne,epoxide,allylic alcohol,carbonyl-related group,and propargylic ester.Meanwhile,the total synthesis of natural products using polyene cyclization as the key step is also listed.The development of efficient synthetic methods is of great significance for natural product synthesis.Although dozens of variants of polyene cyclization have been developed so far,the existing polyene cyclization models still have drawbacks such as a small range of substrate applicability and low similarity to the natural product skeleton.The introduction of the allene group,which has a unique structure and multiple reaction sites,might lead to the development of a new methodology with better extensibility for its products.Based on our previous research results in the field of polyene cyclization,we designed a new model of polyene cyclization reaction using allene group as an initiator and Lewis acid as catalyst to provide a new strategy for the total synthesis of diterpene natural products,and used this reaction as a key step to finished the total synthesis of seven abietane-type diterpenoids.The second part of the thesis presents the total synthesis of the natural product miltiorin A,which belongs to abietane-type diterpenoids with a characteristic 6/6/6tricyclic ring system.Because of the unique biological and pharmacological properties of abietane-type diterpenoids,many synthetic studies have been reported on the modification of this skeleton to obtain new bioactive molecules with potential therapeutic effects.Since the isolation of natural products from nature is normally less efficient,the use of chemical methods to synthesize these molecules is of great importance,especially for the confirmation of new natural products molecular structure.Using an Au-catalyzed 1,3-acyloxy migration/cyclization cascade reaction as the key step,we have completed the first synthesis of miltiorin A with a total yield of 5.4%in nine steps,which provides a material basis for its activity study and reagent development.