UC Irvine

This dissertation describes four research aims involving natural products total synthesis or synthetic methods development. Chapter 1 reviews the isolation, proposed biosynthesis, biological activity, and prior syntheses of pyrroloiminoquinone (PIQ) alkaloids. Chapter 2 describes our efforts towards a synthesis of aleutianamine, a PIQ alkaloid that is structurally distinct from other PIQs and possesses selective anticancer properties. While an aleutianamine synthesis has yet to be accomplished in our laboratory after several synthesis approaches (discussed herein), we discovered novel reactivity of PIQ intermediates en route to aleutianamine, which will aid in our ongoing synthesis efforts. Chapter 3 describes syntheses of numerous simpler PIQ alkaloids, fueled by an efficient synthesis of a versatile PIQ building block en route to aleutianamine. These studies were motivated by a preliminary discovery that some simpler PIQs possess antimalarial properties. By collaborating with the Ben Mamoun and Le Roch groups at Yale and UC Riverside, respectively, we discovered that many of our synthetic PIQs are promising inhibitors of human disease-causing parasites Plasmodium falciparum and Babesia divergens. Chapter 4 describes our synthesis of a monoterpene indole alkaloid alstonlarsine A from alstolucines B and F, which are all isolated from plants of genus Alstonia. The success of our synthesis supports the chemical feasibility of a new biosynthetic proposal for alstonlarsine A. Chapter 5 describes our development of a novel cascade annulation reaction inspired by a bicyclization reaction discovered previously in our lab. In this work, we use similar conditions to react allylbenzenes and electron-deficient alkenes to make functionalized tetralin products.