UC Berkeley

Abstract

A Unified Approach Toward the Total Syntheses of

Prenylated Indole Alkaloid Natural Products

by

Eduardo Valentin Mercado-Marin

Doctor of Philosophy in Chemistry

University of California, Berkeley

Professor Richmond Sarpong, Chair

This dissertation describes our approach toward a unifying synthesis of prenylated indole alkaloid natural products. Chapter 1 is an introduction and provides background to this class of natural products, focusing primarily on the isolation, biological activity, biosynthetic, and previous synthetic work of these natural products. This section also includes a discussion of synthetic approaches to the common bicyclo[2.2.2]diazaoctane core embodied in many of these natural products, which sets the stage for our entry into these molecules by a unifying route.

Chapter 2 describes our entry into this class of natural products focused primarily on our synthetic and biosynthetic work toward natural products lacking the bicyclo[2.2.2]diazaoctane core. In particular, we discuss the first chemical syntheses of the prenylated indole alkaloids citrinalin B and cyclopiamine B. Along with unambiguously establishing the structures of these natural products, in collaboration with the Berlinck group, we provide evidence for the existence of a common bicyclo[2.2.2]diazaoctane containing precursor as an intermediate to natural products that lack this structural feature.

Lastly, Chapter 3 describes our unified strategy for the synthesis of prenylated indole alkaloid natural products, capitalizing on our results described in Chapter 2. This unifying strategy has resulted in the syntheses of stephacidin A and 17-hydroxy-citrinalin B. Key to the success of this approach in accessing congeners containing and lacking the bicyclo[2.2.2]diazaoctane core was a complexity building isocyanate capture to forge the bicyclo[2.2.2]diazaoctane core from a common all fused precursor.