Abstract
<jats:p>The total synthesis of complex natural products remains an important enterprise in chemistry. Beyond providing access to bioactive products and therapeutic leads, these syntheses serve as a historical record of our evolving ability to navigate molecular complexity. Identifying trends in these synthetic campaigns has potential to not only accent areas of current importance but also pinpoint areas that are underdeveloped or underutilized. This study presents a manually curated analysis of natural product total syntheses published in the Journal of the American Chemical Society and Angewandte Chemie International Edition, comparing landmarks from 2003 and 2023. This manually verified dataset captures nuanced shifts in target selection, stereochemical strategy, and synthetic efficiency. Our findings reveal significant transitions in natural product classes and the maturation of asymmetric catalysis, illustrating how modern tools have reshaped synthetic strategy. By documenting these trends through a human-centric lens, this work establishes a benchmark for evaluating synthetic elegance and provides a foundational template to inform future computer-guided synthetic analysis.</jats:p>