Conquering peaks and illuminating depths: developing stereocontrolled organic reactions to unlock nature's macrolide treasure trove

The structural complexity and biological importance of macrolide natural products has inspired the development of innovative strategies for their chemical synthesis. With their dense stereochemical content, high level of oxygenation and macrocyclic cores, we viewed the efficient total synthesis of these valuable compounds as an aspirational driver towards developing robust methods and strategies for their construction. Starting out from the initial development of our versatile asymmetric aldol methodology, this personal perspective reflects on an adventurous journey, with all its trials, tribulations and serendipitous discoveries, across the total synthesis, in our group, of a representative selection of six macrolide natural products of marine and terrestrial origin - swinholide A, spongistatin 1, spirastrellolide A, leiodermatolide, chivosazole F and actinoallolide A.

Automated summary

This article explores innovative strategies for the chemical synthesis of macrolide natural products and reflects on the challenges and discoveries encountered during the total synthesis process in the laboratory. By synthesizing six representative macrolide natural products, researchers propose efficient methods for the construction of these valuable compounds.