retrosynthesis

name	retrosynthesis
description	Plan synthetic routes and judge whether a proposed molecule can actually be made, using AiZynthFinder's Monte-Carlo tree search over template-derived reactions and a purchasable building-block stock. Use this skill to configure expansion and filter policies, choose a stock file, run route search over a candidate set, and read the returned trees — solved fraction, route depth, and which building blocks a route bottoms out in. Also trigger on AiZynthFinder, retrosynthetic tree search, synthetic accessibility, SAscore, RAscore, building-block stock, reaction template, or route scoring.
license	MIT
allowed-tools	Read Write Edit Bash
compatibility	Requires Python 3.10+. The bundled scripts write AiZynthFinder YAML configuration and parse its route JSON using only the standard library. Running a search needs aizynthfinder 4.4+ (pip, Python >=3.10 and <3.13, MIT) plus its downloaded policy models and a stock file; CPU is sufficient, though a GPU speeds up the expansion policy.
metadata	{"version":"1.0","skill-author":"K-Dense Inc.","openclaw":{"emoji":"⚗️","homepage":"https://github.com/MolecularAI/aizynthfinder"},"hermes":{"category":"research"}}

Retrosynthetic Planning

The Make half of design-make-test-analyse, and the check that a proposed molecule is more than a picture. AiZynthFinder runs Monte Carlo tree search over reaction templates until every leaf of a route is something you can buy.

Tool: AiZynthFinder 4.4.1, MIT. pip install aizynthfinder — Python 3.10–3.12 only, it will not install on 3.13. Then download_public_data <dir> for models and a ZINC stock (several GB). CPU is sufficient. Checked against: 4.4.1, December 2025.

Read references/aizynthfinder-setup.md before your first run, references/synthesizability-scores.md when triaging more molecules than you can search, and references/route-quality.md before acting on a route — that one is judgement, not syntax.

The two scripts

Script	Answers
aizynth_config.py	What does the config look like, and are the model files really there?
route_report.py	What fraction is makeable, in how many steps, from what?

The stock file is the answer

This is the thing to get right. A target is solved when every leaf of a route is in your stock file — so "solved" is a statement about the stock at least as much as about the molecule.

Stock	Solved fraction
small in-house inventory	low; reflects what you can start today
ZINC (the default download)	moderate; a public baseline
eMolecules / commercial	high
Enamine building blocks	high; what a REAL-space campaign should use

A solved fraction quoted without naming the stock is meaningless — the same molecule is solved against eMolecules and unsolved against a cupboard. route_report.py says so on every run.

Configuration changed at version 4

Version 3 took bare lists of file paths; version 4 takes typed blocks. Every tutorial older than 2024 shows the incompatible form, and the resulting error is unhelpful.

python skills/retrosynthesis/scripts/aizynth_config.py config \
    --model uspto_model.onnx --templates uspto_templates.csv.gz \
    --filter-model uspto_filter_model.onnx --stock zinc:zinc_stock.hdf5 > config.yml
python skills/retrosynthesis/scripts/aizynth_config.py check --config config.yml