EvolvedComplexity as a Total Synthesis Assessment Metric: Strychnine as a Case Study of Scoring Functions
The selection of synthetic routes to a small molecule of interest is enabled by the use of various tools to assess the chemical complexity of a given intermediate. While prior approaches assess the intrinsic molecular complexity or the facility with which an intermediate can be synthesized, in this study, we introduce an alternative approach that tracks the progress toward the target structure in a given synthesis. A simple metric, EvolvedComplexity, was developed that compares the chemical similarity of a pair of molecules on the basis of the Tanimoto distance between chemical fingerprints. This complementary approach to assessing progress in the synthesis may prove to be a useful tool for planning synthetic routes and developing novel chemistries.
Authors
- Frédéric G. Buono (ORCID: https://orcid.org/0000-0001-7585-0438)
- Abbigayle E. Cuomo (ORCID: https://orcid.org/0000-0003-2117-0925)
- Yu Shee (ORCID: https://orcid.org/0000-0002-3728-0021)
- Sumon Sarkar (ORCID: https://orcid.org/0000-0001-9246-3261)
- Timothy R. Newhouse (ORCID: https://orcid.org/0000-0001-8741-7236)
- H. Ray Kelly (ORCID: https://orcid.org/0000-0003-3811-0662)
- Haote Li (ORCID: https://orcid.org/0000-0002-8146-5066)
- John-Paul Webster (ORCID: https://orcid.org/0000-0001-5486-6203)
- Víctor S. Batista (ORCID: https://orcid.org/0000-0002-3262-1237)
- Sanil Sreekumar (ORCID: https://orcid.org/0009-0005-4497-4661)
Institutions
- Yale University (US)
- Boehringer Ingelheim (Taiwan) (TW)
- Boehringer Ingelheim (Brazil) (BR)
- Boehringer Ingelheim (Japan) (JP)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2025-10-10
- DOI
- https://doi.org/10.1021/acs.joc.5c01393
- Primary Topic
- Chemical synthesis and alkaloids
- Type
- article
- Field-Weighted Citation Impact
- 0.00