Total Synthesis Of Indole Alkaloids: Based On Direct Construction Of Pyrrolocarbazole Scaffolds Via Gold-catalyzed Cascade Cyclizations (springer Theses)

This book explores efficient syntheses of indole alkaloids based on gold-catalyzed cascade cyclizations, presenting two strategies for total synthesis of these natural products based on gold-catalyzed reactions of conjugated diyne or ynamide. The book first describes the total and formal synthesis of dictyodendrins A–F based on direct construction of the pyrrolo[2,3-c]carbazole core using the gold-catalyzed annulation of azido-diynes and protected pyrrole. This synthetic strategy features late-stage functionalization of the pyrrolo[2,3-c]carbazole scaffold at several positions and allows diverse access to dictyodendrins and their derivatives. Secondly, the book discusses the formal synthesis of vindorosine based on the pyrrolo[2,3-d]carbazole construction using the gold-catalyzed cascade cyclization of ynamide. Importantly, the reaction using a chiral gold complex provides the optically active pyrrolo[2,3-d]carbazole. This strategy facilitates the rapid construction of the pyrrolocarbazole core structure of aspidosperma and related alkaloids, including vindorosine. These methodologies can accelerate the medicinal application of pyrrolocarbazole-type alkaloids and related compounds. Supervisor’s Foreword List of Publications Acknowledgements Contents 1 Introduction 1.1 Pyrrolocarbazoles 1.1.1 Dictyodendrins 1.1.2 Vindorosine 1.2 Gold-Catalyzed Reactions of Alkynes 1.2.1 Gold-Catalyzed Reactions of Ynamides 1.2.2 Gold-Catalyzed Cyclization of Diynes 1.2.3 Gold-Catalyzed Cyclization via Gold Carbenoid Species 1.2.4 Gold-Catalyzed Acetylenic Schmidt Reaction via Gold Carbenoid Species References 2 Total Synthesis of Dictyodendrins by the Gold-Catalyzed Cascade Cyclization of Conjugated Diynes with Pyrroles 2.1 Experimental Section 2.1.1 General Methods 2.1.2 Preparation of the Cyclization Precursors 7 2.1.3 Gold-Catalyzed Cascade Cyclization 2.1.4 Total and Formal Synthesis of Dictyodendrins A–F 2.1.5 Preparation of Catalyst 2.1.6 Biological Evaluations and Binding Mode Analysis References 3 Construction of the Pyrrolo[2,3-d]Carbazole Core of Spiroindoline Alkaloids by Gold-Catalyzed Cascade Cyclization of Ynamide 3.1 Experimental Section 3.1.1 General Methods 3.1.2 Preparation of the Cyclization Precursor 3.1.3 Gold-Catalyzed Cascade Cyclization 3.1.4 Formal Synthesis of Vindorosine 3.1.5 Crystallography References 4 Conclusion