Daniel Armstrong

Daniel Armstrong, Zlatko Jončev, Andres M Bran et al.

Modern computer-assisted synthesis planning (CASP) systems show promises at generating chemically valid reaction steps but struggle to incorporate strategic considerations such as convergent assembly, protecting group minimization, and optimal ring-forming sequences. We introduce a methodology that leverages Large Language Models to distill synthetic knowledge into code. Our system analyzes synthesis routes and translates strategic principles into Python functions representing diverse strategic and tactical rules, such as strategic functional group interconversions and ring construction strategies. By formalizing this knowledge as verifiable code rather than simple heuristics, we create testable, interpretable representations of synthetic strategy. We release the complete codebase and the USPTO-ST dataset -- synthesis routes annotated with strategic tags. This framework unlocks a novel capability for CASP: natural language-based route retrieval, achieving 75\% Top-3 accuracy on our benchmark. We further validate our library through temporal analysis of historical trends and chemically intuitive route clustering that offers more granular partitioning than common previous methods. This work bridges the tactical-strategic divide in CASP, enabling specification, search, and evaluation of routes by strategic criteria rather than structure alone.

Nguyen Xuan-Vu, Daniel Armstrong, Milena Wehrbach et al.

Computer-aided synthesis planning (CASP) has long been envisioned as a complementary tool for synthetic chemists. However, existing frameworks often lack mechanisms to allow interaction with human experts, limiting their ability to integrate chemists' insights. In this work, we introduce Synthelite, a synthesis planning framework that uses large language models (LLMs) to directly propose retrosynthetic transformations. Synthelite can generate end-to-end synthesis routes by harnessing the intrinsic chemical knowledge and reasoning capabilities of LLMs, while allowing expert intervention through natural language prompts. Our experiments demonstrate that Synthelite can flexibly adapt its planning trajectory to diverse user-specified constraints, achieving up to 95\% success rates in both strategy-constrained and starting-material-constrained synthesis tasks. Additionally, Synthelite exhibits the ability to account for chemical feasibility during route design. We envision Synthelite to be both a useful tool and a step toward a paradigm where LLMs are the central orchestrators of synthesis planning.

Daniel Armstrong, Zlatko Joncev, Jeff Guo et al.

Computer-aided synthesis planning (CASP) has made significant strides in generating retrosynthetic pathways for simple molecules in a non-constrained fashion. Recent work introduces a specialised bidirectional search algorithm with forward and retro expansion to address the starting material-constrained synthesis problem, allowing CASP systems to provide synthesis pathways from specified starting materials, such as waste products or renewable feed-stocks. In this work, we introduce a simple guided search which allows solving the starting material-constrained synthesis planning problem using an existing, uni-directional search algorithm, Retro*. We show that by optimising a single hyperparameter, Tango* outperforms existing methods in terms of efficiency and solve rate. We find the Tango* cost function catalyses strong improvements for the bidirectional DESP methods. Our method also achieves lower wall clock times while proposing synthetic routes of similar length, a common metric for route quality. Finally, we highlight potential reasons for the strong performance of Tango over neural guided search methods

Daniel Armstrong, André Jonasson

In this paper, we present a new algorithm that extends RRT* and RT-RRT* for online path planning in complex, dynamic environments. Sampling-based approaches often perform poorly in environments with narrow passages, a feature common to many indoor applications of mobile robots as well as computer games. Our method extends RRT-based sampling methods to enable the use of an assisting distance metric to improve performance in environments with obstacles. This assisting metric, which can be any metric that has better properties than the Euclidean metric when line of sight is blocked, is used in combination with the standard Euclidean metric in such a way that the algorithm can reap benefits from the assisting metric while maintaining the desirable properties of previous RRT variants - namely probabilistic completeness in tree coverage and asymptotic optimality in path length. We also introduce a new method of targeted rewiring, aimed at shortening search times and path lengths in tasks where the goal shifts repeatedly. We demonstrate that our method offers considerable improvements over existing multi-query planners such as RT-RRT* when using diffusion distance as an assisting metric; finding near-optimal paths with a decrease in search time of several orders of magnitude. Experimental results show planning times reduced by 99.5% and path lengths by 9.8% over existing real-time RRT planners in a variety of environments.