Total Synthesis of Complex Natural Products: More Than a Race for Molecular Summits
Sarah E. Reisman, Thomas J. Maimone
Abstract
A particularly rich chapter in the ongoing story of organic chemistry, a field nearly two centuries old, is that of natural products total synthesis. Over the past century, total synthesis has served as a general testing ground and indicator of the capabilities of organic synthesis while also synergizing with the areas of physical organic chemistry, spectroscopy, and transition metal catalysis, among others. Many highly complex natural products, including some previously considered unfathomable as synthetic targets just decades prior, have been prepared through fully synthetic processes. Additionally, advances in stereoselective methodology and asymmetric catalysis have allowed for many highly enantioselective syntheses, a feature of significant importance for translational applications because a single enantiomer of the natural product is typically biologically active. Indeed, advances in total synthesis can be seen in multiple facets of modern-day drug discovery, whether it be complex payloads for antibody–drug conjugates, probes for target identification and mechanism of action studies, or for the synthesis of FDA-approved medicines themselves.