Chapter 1 Gold Catalysis: Strategic Advantages in the Total Syntheses of Complex Natural Products Since its early use in the late 1980 and 1990, homogeneous gold catalysis has emerged as a powerful tool in the field of natural product synthesis. Herein, we illustrated with recent examples that the incorporation of gold catalysis in total synthesis has benefited tremendously in the rapid construction of challenging all-carbon quaternary centers and medium-sized ring. Chapter 2 Formal Synthesis of (+)-Strictamine Strictamine is a pentacyclic Akuammiline alkaloid isolated in 1966 bearing a unique methanoquinolizidine core and its total synthesis puzzle has not been solved for 50 years. While a number of total and formal syntheses of strictamine were discloses by other labs in recent years, all of them required no less than 14 steps of chemical transformations. We developed a gold-catalyzed 6-endo-dig cyclization with “protonation as traceless protection” strategy to access the key intermediate towards strictamine and accomplished a concise formal synthesis of strictamine (6 step racemic, 7 step asymmetric). The application of an enantioselective propargylation developed during the course of our research was also demonstrated in the catalytic asymmetric synthesis of other indole alkaloids. Chapter 3 Total Synthesis of (+)-Arborisidine Arborisidine is a pentacyclic indole alkaloid isolated in 2016 containing a rare fully substituted cyclohexanone moiety, with promising in vitro inhibition activity of gastric cancer in combination of pimelautide. The presence of aza-quaternary center and dense substitutions raised significant synthetic challenges. Herein, we discussed our elaborations of 6-endo-dig cyclization reactions and detours to access the intriguing core of arborisidine, and additional efforts in the regioselective functionalization of dienes as well as late-stage one-pot redox manipulations, which ultimately led to the first total synthesis of arborisidine (7 steps racemic, 9 steps asymmetric). The development of chemoselective decyanation reaction also provided alternative entry to the enantioenriched 1-acyl tetrahydro-β-carboline building blocks. Chapter 4 Studies toward Total Synthesis of Harziane Diterpenes Harziane diterpenes, mostly isolated from Trichoderma fungi species, constitute of a considerable number of members sharing a complicated tetracyclic scaffold with four-, five-, six- and seven membered rings, at least five stereocenters and three all-carbon quaternary centers, in which two are vicinal. We designed a unified approach taking advantage of the gold-catalyzed [2+2] cycloaddition reaction to access the unique 7-4 fused bicyclic system with different types of ring tethers. A ring reorganization strategy was also devised, complementary to the innate selectivity of Favorskii-type ring contraction. These establishments allowed access to a key ketoaldehyde intermediate in 10 steps that contains the major stereocenters in the right half of harziane diterpenes. With the aid of versatile diene functionalizations, we would hopefully complete the collective total synthesis of harziane diterpene natural products in the near future.



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