In a 2023 Science paper, researchers utilized SYNTHIA^® Retrosynthesis Software to significantly reduce the steps needed to synthesize stemoamide. The study highlights the importance of efficient chemical synthesis to meet future demands in medicine, materials, and agrochemicals. Traditionally, retrosynthetic analysis of complex molecules faced challenges due to the vast number of possible routes, overwhelming computer systems. This research merges computer-aided synthesis planning with molecular graph editing to streamline the synthesis of alkaloids, culminating in an enantioselective three-step synthesis of (–)-stemoamide by identifying high-impact key steps through graph edit distances.

The sophistication of software predicting synthetic routes for complex molecules is rapidly advancing, yet the extent to which these algorithms replicate or complement human intuition remains uncertain. Lin et al. tested a commercial retrosynthesis program with an alkaloid that had over 30 documented syntheses. The algorithm uniquely proposed a Mannich reaction not previously used, though human intervention improved other aspects of the route. By developing a graph-based method to prioritize key steps, the authors achieved the shortest synthesis of this target.

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Yingfu Lin et al. ,
Computer-aided key step generation in alkaloid total synthesis.
Science 379,453-457(2023). DOI:10.1126/science.ade8459