EvolvedComplexity as a Total Synthesis Assessment Metric: Strychnine as a Case Study of Scoring Functions

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Synthetic Chemistry

Background:

• Selecting optimal synthetic routes is crucial for small molecule synthesis.
• Existing tools often focus on intermediate complexity or ease of synthesis.
• A gap exists in methods that track progress toward a specific target molecule during synthesis.

Purpose of the Study:

• To introduce a novel approach for assessing synthetic route efficiency.
• To develop a metric that quantifies progress towards a target molecule.
• To provide a complementary tool for synthetic planning and chemical innovation.

Main Methods:

• Developed a metric termed EvolvedComplexity.
• Quantified molecular similarity using Tanimoto distance between chemical fingerprints.
• Applied the metric to compare pairs of molecules within a synthetic pathway.

Main Results:

• EvolvedComplexity provides a measure of synthetic progression.
• The metric offers an alternative perspective to intrinsic molecular complexity.
• Demonstrated the utility of tracking similarity for evaluating synthetic steps.

Conclusions:

• EvolvedComplexity is a valuable tool for synthetic route planning.
• This metric can assist in the development of new synthetic methodologies.
• The approach complements existing methods for assessing chemical synthesis.