# From Feasible to Practical: Pareto-Optimal Synthesis Planning

arXiv: https://arxiv.org/abs/2605.07521 · HTML: https://mlsanity.com/paper/2605.07521/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 14 of its 48 references that are in the map.
- First posted on arXiv 8 May 2026.

## Builds on (most cited first, 14 of 14)

- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
- [Learning to Plan Chemical Syntheses](https://mlsanity.com/paper/1708.04202/) (2017)
- [Retrosynthesis Prediction with Conditional Graph Logic Network](https://mlsanity.com/paper/2001.01408/) (2020)
- [Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Edits](https://mlsanity.com/paper/2006.15426/) (2020)
- [Retro*: Learning Retrosynthetic Planning with Neural Guided A* Search](https://mlsanity.com/paper/2006.15820/) (2020)
- [Learning Graph Models for Retrosynthesis Prediction](https://mlsanity.com/paper/2006.07038/) (2020)
- [GIBBON: General-purpose Information-Based Bayesian OptimisatioN](https://mlsanity.com/paper/2102.03324/) (2021)
- [RetroGraph: Retrosynthetic Planning with Graph Search](https://mlsanity.com/paper/2206.11477/) (2022)
- [Double-Ended Synthesis Planning with Goal-Constrained Bidirectional Search](https://mlsanity.com/paper/2407.06334/) (2024)
- [Self-Improved Retrosynthetic Planning](https://mlsanity.com/paper/2106.04880/) (2021)
- [Retrosynthetic Planning with Dual Value Networks](https://mlsanity.com/paper/2301.13755/) (2023)
- [Retro-fallback: retrosynthetic planning in an uncertain world](https://mlsanity.com/paper/2310.09270/) (2023)
- [Tango*: Constrained synthesis planning using chemically informed value functions](https://mlsanity.com/paper/2412.03424/) (2024)
- [Retrosynthesis Planning via Worst-path Policy Optimisation in Tree-structured MDPs](https://mlsanity.com/paper/2509.10504/) (2025)

## Built on by (most cited first, 2 of 2)

- [Coverage Before Control: Route-Instruction Grounding and Steering for Controllable Retrosynthesis](https://mlsanity.com/paper/2609.39955/) (2026)
- [RetroPlanner: Multi-Route Expansion and Multi-Objective Reasoning for LLM-Based Retrosynthesis Planning](https://mlsanity.com/paper/2610.16391/) (2026)

## Abstract (arXiv)

Current computer-aided synthesis planning (CASP) methods often treat retrosynthesis as solved once a single feasible route is identified, focusing primarily on convergence or shortest-path metrics. This view is misaligned with real-world practice, where chemists must balance competing objectives such as cost, sustainability, toxicity, and overall yield. To address this, we formulate synthesis planning as a multi-objective search problem and introduce MORetro*, an algorithm that generates a Pareto front of synthesis routes to explicitly capture trade-offs among user-defined criteria. MORetro* uses weighted scalarization and BO-informed sampling to efficiently navigate the combinatorial search space and prioritize promising trade-offs. Building on multi-objective A*-search, we provide optimality guarantees showing that, for a fixed single-step model, MORetro* recovers the true Pareto front under admissibility. Across multiple retrosynthesis benchmarks, MORetro* produces diverse, high-quality Pareto fronts, uncovering solutions overlooked by single-objective approaches and better aligning CASP outputs with industrial decision-making.