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Main Authors: Hastedt, Friedrich, Zhang, Dongda, Chanona, Antonio del Rio
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2605.07521
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author Hastedt, Friedrich
Zhang, Dongda
Chanona, Antonio del Rio
author_facet Hastedt, Friedrich
Zhang, Dongda
Chanona, Antonio del Rio
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2605_07521
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle From Feasible to Practical: Pareto-Optimal Synthesis Planning
Hastedt, Friedrich
Zhang, Dongda
Chanona, Antonio del Rio
Artificial Intelligence
I.2.1
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.
title From Feasible to Practical: Pareto-Optimal Synthesis Planning
topic Artificial Intelligence
I.2.1
url https://arxiv.org/abs/2605.07521