Procrustean Bed for AI-Driven Retrosynthesis: A Unified Framework for Reproducible Evaluation

Fuente: arXiv
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Main Authors: Morgunov, Anton, Batista, Victor S.
Format: Preprint
Published: 2025
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author Morgunov, Anton
Batista, Victor S.
author_facet Morgunov, Anton
Batista, Victor S.
contents Progress in computer-aided synthesis planning (CASP) is obscured by the lack of standardized evaluation infrastructure and the reliance on metrics that prioritize topological completion over chemical validity. We introduce RetroCast, a unified evaluation suite that standardizes heterogeneous model outputs into a common schema to enable statistically rigorous, apples-to-apples comparison. The framework includes a reproducible benchmarking pipeline with stratified sampling and bootstrapped confidence intervals, accompanied by SynthArena, an interactive platform for qualitative route inspection. We utilize this infrastructure to evaluate leading search-based and sequence-based algorithms on a new suite of standardized benchmarks. Our analysis reveals a divergence between "solvability" (stock-termination rate) and route quality; high solvability scores often mask chemical invalidity or fail to correlate with the reproduction of experimental ground truths. Furthermore, we identify a "complexity cliff" in which search-based methods, despite high solvability rates, exhibit a sharp performance decay in reconstructing long-range synthetic plans compared to sequence-based approaches. We release the full framework, benchmark definitions, and a standardized database of model predictions to support transparent and reproducible development in the field.
format Preprint
id arxiv_https___arxiv_org_abs_2512_07079
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Procrustean Bed for AI-Driven Retrosynthesis: A Unified Framework for Reproducible Evaluation
Morgunov, Anton
Batista, Victor S.
Machine Learning
Artificial Intelligence
Progress in computer-aided synthesis planning (CASP) is obscured by the lack of standardized evaluation infrastructure and the reliance on metrics that prioritize topological completion over chemical validity. We introduce RetroCast, a unified evaluation suite that standardizes heterogeneous model outputs into a common schema to enable statistically rigorous, apples-to-apples comparison. The framework includes a reproducible benchmarking pipeline with stratified sampling and bootstrapped confidence intervals, accompanied by SynthArena, an interactive platform for qualitative route inspection. We utilize this infrastructure to evaluate leading search-based and sequence-based algorithms on a new suite of standardized benchmarks. Our analysis reveals a divergence between "solvability" (stock-termination rate) and route quality; high solvability scores often mask chemical invalidity or fail to correlate with the reproduction of experimental ground truths. Furthermore, we identify a "complexity cliff" in which search-based methods, despite high solvability rates, exhibit a sharp performance decay in reconstructing long-range synthetic plans compared to sequence-based approaches. We release the full framework, benchmark definitions, and a standardized database of model predictions to support transparent and reproducible development in the field.
title Procrustean Bed for AI-Driven Retrosynthesis: A Unified Framework for Reproducible Evaluation
topic Machine Learning
Artificial Intelligence
url https://arxiv.org/abs/2512.07079