The Stereocontrolled Total Synthesis of Polyketide Natural Products: A Thirty-Year Journey

Abstract

Abstract The diverse and complex structures of polyketide natural products have stimulated the imagination of synthetic chemists for decades. Captivated by their often impressive biological activities and their dazzling array of stereochemically-rich motifs, we have been motivated to achieve their efficient and stereocontrolled total synthesis. This review captures snapshots from our thirty-year foray into the total synthesis of 18 polyketide natural products, detailing the unique challenges, discoveries and revelations made en route to eventual success. Notably, crucial to each of these campaigns was the judicious application of highly selective aldol reactions to iteratively configure the densely oxygenated stereoclusters that characterise this fascinating class of bioactive natural products.