From grimoire
Plans multi-step chemical syntheses via retrosynthetic analysis, working backward from target molecule to available starting materials.
How this skill is triggered — by the user, by Claude, or both
Slash command
/grimoire:design-synthesis-routeThe summary Claude sees in its skill listing — used to decide when to auto-load this skill
Plan an efficient, feasible multi-step synthesis by working backward from target to available starting materials using retrosynthetic analysis.
Plan an efficient, feasible multi-step synthesis by working backward from target to available starting materials using retrosynthetic analysis.
Adopted by: Pharmaceutical process chemistry (FDA IND submissions), ACS Division of Organic Chemistry, Harvard/MIT/Caltech graduate synthesis courses, SciFinder and Reaxys route-planning algorithms.
Impact: Retrosynthetic analysis by Corey (Nobel Prize 1990) reduced average synthesis step count by 30–50% in complex natural product total synthesis; computer-assisted retrosynthesis (ASKCOS, ICSYNTH) achieves 80%+ accuracy for multi-step routes.
Why best: Working backward from target prevents forward-synthesis dead ends; disconnection approach systematically identifies bond-forming reactions, reducing reliance on intuition.
Sources: Corey & Cheng (1989) chapters 1–5; Warren & Wyatt 2nd ed. (2008); Clayden "Organic Chemistry" 2nd ed. (2012) ch. 30–31.
Draw the target molecule (TM) — use skeletal structure; identify all functional groups, stereocenters, and ring systems.
Assess complexity — count carbons, stereocenters (n stereocenters → up to 2ⁿ stereoisomers), functional group count, and ring strain. Estimate required step count (~1–3 steps per complexity unit).
Identify key disconnections — apply retrosynthetic arrow (⟹) to break strategic bonds: bonds α to functional groups, bonds that simplify ring systems, bonds in the longest carbon chain.
Apply transform library — for each disconnection, identify the corresponding forward reaction: Diels-Alder (for 6-membered rings), aldol (for β-hydroxy carbonyls), Wittig/HWE (for alkenes), cross-coupling (for C–C/C–heteroatom bonds), etc.
Generate synthons and reagent equivalents — convert each synthon to a real reagent (e.g., acyl cation synthon → acyl chloride + Lewis acid; carbanion synthon → organolithium or Grignard).
Evaluate each route — score on: (a) step count (fewer = better), (b) overall yield estimate (product of step yields), (c) reagent cost and availability, (d) stereochemical control, (e) scalability and safety.
Check literature precedent — search SciFinder or Reaxys for each proposed step; confirm reaction conditions, yield range, and functional group compatibility. Prefer reactions with >70% reported yield.
Write forward synthesis — convert the retrosynthetic tree to a forward synthesis scheme with reagents, conditions, solvents, and expected yields per step.
Identify protecting group strategy — plan installation and removal of protecting groups for sensitive functional groups; use minimal number of protecting group operations.
Flag safety and scale concerns — identify hazardous reagents (organolithiums, azides, peroxides), exothermic steps, and steps unsuitable for scale-up.
npx claudepluginhub jeffreytse/grimoire --plugin grimoireReasons from first principles to predict reaction products, analyze mechanisms, and interpret NMR/IR/MS spectra for organic synthesis problems.
Evaluates chemical syntheses and processes using the 12 Principles of Green Chemistry to minimize waste, hazards, energy use, and environmental impact.
Provides the RDKit cheminformatics toolkit for molecular parsing, descriptor calculation, fingerprinting, substructure search, 2D/3D coordinate generation, similarity, and reaction handling. Use when advanced control or custom algorithms are needed.