The structural prominence of indole-based sulfur-containing compounds in pharmacologically relevant substances stems from their versatile biofunctional capabilities. Despite their significance, the st...

An approach that combines single-nucleus RNA sequencing and multiplexed perturbation identifies genes that enable the biosynthesis of direct precursors of the anti-cancer drug Taxol, whose curren...

Die Herstellung von bioaktiven Molekülen und Arzneimitteln könnte künftig ohne externe Enzym- oder Metallkatalysatoren auskommen. Chemiker/-innen der Friedrich-Alexander-Universität Erlangen-Nürnberg…

Fully automated preparation of diverse small organic molecules remains a formidable challenge due to the inherent constraints of conventional synthetic philosophies. The existing automation approaches require access to either almost unlimited kinds of chemical reagents or custom-made building blocks (BBs). Herein we propose atom-by-atom iterative synthesis (AIS) as a new synthetic logic to tackle this challenge. By viewing complex organic molecules as assemblies of single-carbon- or heteroatom-based units, AIS aims to construct molecular skeletons through iterative coupling of simple atomic-scale BBs by a unified type of reaction─boron homologations. Compared with conventional approaches, the AIS strategy uses only a few types of chemical reactions and a small set of BBs, making it more suitable for automation and artificial intelligence-assisted synthetic route design. To date, enormous progresses have been made on the synthetic chemistry that serves for the purpose of AIS, such as introducing heteroatoms and sp2-carbons, forming ring structures, developing thermostable carbenoid reagents, and achieving stereochemical controls. On the other hand, substantial challenges and limitations remain to be overcome for realizing fully automated construction of diverse molecules. This Outlook article describes the AIS concept, recent progress, current limitations, and future opportunities in this field.

In the future, it may be possible to produce bioactive molecules and pharmaceuticals without reverting to using enzymes or metals as external catalysts.