Strategies and Tactics in Alkaloid Synthesis: Total Synthesis of Strempeliopidine via a Non-Directed Petasis Reaction and Progress Toward the Synthesis of Mitomycin B

This thesis describes research toward total synthesis of bioactive alkaloids with complex architectures that have demanded for the invention of methodology. Chapter 1 comprehensively reviews the semi-, partial, and total synthesis of heterodimeric monoterpenoid bisindole alkaloid natural products. Chapter 2 describes the enantioselective total synthesis of the bisindole alkaloid strempeliopidine. A convergent strategy featuring a diastereoselective Petasis reaction enabled the synthesis of the natural product and several stereoisomeric analogs. Chapter 3 details the development of a non-directed Petasis reaction inspired by the key step in the synthesis of strempeliopidine. This methodology couples hydroxyindoles with trifluoroborate salts under mild conditions, thereby enabling the synthesis of non-natural heterodimeric bisindole alkaloids. Chapter 4 explores ongoing efforts toward the asymmetric total synthesis of mitomycin B. Chapter 5 covers the development of an enantioselective 1,3-dipolar cycloaddition for the construction of nitrogen-rich spirocycles. A chiral magnesium Lewis acid catalyst facilitated the asymmetric [3+2] cycloaddition between alpha-methylene lactams and diazoacetates or nitrile oxides.