Plan a Synthesis Route (Retrosynthesis)

What you'll accomplish

By the end of this guide, you'll have drawn a target molecule, asked the AI for retrosynthetic routes, and understood how to interpret the step-by-step suggestions. You'll also know the limitations of AI-suggested routes and when to verify against literature.

What is retrosynthesis?

Retrosynthesis is the process of working backward from a target molecule to identify a sequence of reactions that could produce it from simpler, commercially available starting materials. Each step "disconnects" a bond or functional group, revealing a simpler precursor.

This approach was formalized by E.J. Corey in the 1960s and remains the foundation of synthetic planning in organic chemistry. ChemStitch's AI applies this reasoning computationally, suggesting disconnections based on known reaction types.

Step 1: Draw your target molecule

Draw the molecule you want to synthesize on the canvas. You can build it from scratch with bond tools and templates, import it from a MOL or SMILES file, or look it up via PubChem.

For best results, draw a complete structure with correct stereochemistry. The AI's suggestions are only as good as the structural input.

Step 2: Ask for synthetic routes

In the chat panel, type something like: "How would I synthesize this molecule?" or "Suggest a retrosynthetic route for this structure." The AI analyzes your target and proposes one or more synthetic routes.

Routes are displayed as step-by-step sequences. Each step shows the transformation, reagents/conditions, and intermediate structures leading back to starting materials.

Step 3: Evaluate the suggestions

Retrosynthesis suggestions carry the AI Suggested confidence level (yellow badge). This is important: the AI is proposing plausible routes based on pattern recognition, not guaranteeing that a reaction will work in your specific conditions.

When evaluating a suggested route, consider:

• • Are the starting materials commercially available? — Check supplier catalogs (Sigma-Aldrich, TCI, Alfa Aesar) for the proposed starting materials.
• • Are the reaction conditions practical? — Some AI-suggested transformations may require extreme temperatures, expensive catalysts, or anhydrous conditions that are impractical for your lab.
• • Is the selectivity realistic? — If a step involves a molecule with multiple reactive sites, consider whether the suggested selectivity is achievable.
• • What is the expected yield? — The AI does not predict yields. Literature precedent for similar transformations is your best guide.

Step 4: Iterate and refine

You can ask follow-up questions to refine the route: "Can you suggest an alternative to the Grignard step?" or "What if I want to avoid using palladium catalysts?" The AI generates alternative disconnections based on your constraints.

You can also draw an intermediate on the canvas and ask the AI how to convert it to the next intermediate in the route. This step-by-step approach is useful for complex multi-step syntheses.

Combining retrosynthesis with property prediction

A common medicinal chemistry workflow: draw a target, check its drug-likeness properties (see the Predict Drug-Likeness guide), then plan a synthesis route. If the target fails Lipinski criteria, you can modify the structure on the canvas, re-check properties, and plan a new route — all without leaving ChemStitch.

Limitations to keep in mind

AI retrosynthesis is a planning aid, not a substitute for synthetic expertise. The suggestions are based on pattern matching against known reactions, and they do not account for every practical consideration (scale, safety, cost, environmental impact).

Always verify AI-suggested routes against literature before committing to a synthesis. SciFinder, Reaxys, and the primary literature remain the authoritative sources for reaction precedent.