Extended Data Fig. 9: Pathways leading to ramelteon designed by the software with and without multistep strategizing routines.
From: Computational planning of the synthesis of complex natural products
The top synthetic pathway was designed without the new, multistep heuristics. The scaffold of the target was constructed via Cu-catalysed hydroalkylation of alkenes68. Although the pathway does not contain chemically erroneous steps, it is long, relies heavily on reductions and oxidations, and involves many FGIs. The bottom route, designed with the new strategizing routines, is more concise and elegant. The key element in this path is a strategy that relies on Robinson annulation followed by dehydrogenation of enones (in the retrosynthetic direction, when planning the route, the program strategizes and first performs a seemingly unproductive dearomatization of a phenol, which then enables Robinson annulation).
