In new research, Professor Richmond Sarpong and his co-researchers (DOI: 10.1021/jacs.1c00293), have developed concise total syntheses of the natural products cephanolides A—D utilizing retrosynthesis guided by chemical network analysis which successfully identified important and strategic bonds. The chemical synthesis approach constructs the cephanolide skeletal framework by employing a simple cross-coupling followed by an intramolecular inverse-demand Diels-Alder cycloaddition. The researchers employed late-stage oxygenation to achieve structural diversification, setting the stage for the preparation of other structurally similar natural products.

The cephanolides are related to another natural product called harringtonolide, which shows nanomolar activity against cancer cell lines (KB cells). As such, they have the potential to serve as tools to better understand the underlying mechanisms for the anticancer activity of the larger family of related natural products.