Chemical Synthesis Route Selection Using Molecular Graph Editing
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Solution Overview
Problem
Existing computer-aided synthesis planning (CASP) strategies prioritize well-precedented reactions for reliability, often leading to inefficient and costly synthesis processes with excessive protecting group manipulations and low impact steps, failing to leverage high-impact key steps effectively.
Innovation Solution
A method that combines high-throughput computer-aided synthesis planning with molecular graph editing to identify and combine high-impact steps from multiple routes, minimizing synthetic steps and optimizing the synthesis process for complex molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CASP strategies prioritize well-precedented reactions for reliability, then reaction reliability is improved, but synthesis efficiency and productivity deteriorate due to excessive steps and low impact operations
Solution Approach 1:
The patent replaces traditional rule-based CASP systems with a graph edit distance-based system. Instead of relying on pre-encoded reaction rules that favor well-precedented reactions, the new system uses graph theory to evaluate and compare synthetic routes objectively, identifying high-impact steps that maximize structural complexity generation while minimizing protecting group manipulations and low-impact operations.
Solution Approach 2:
The patent changes the evaluation parameters from reaction reliability metrics to graph edit distance metrics. By quantifying the impact of each synthetic step through graph edit distances between molecular graphs, the system can identify and prioritize high-impact steps that form multiple target bonds simultaneously, thereby improving productivity while maintaining reliability through systematic evaluation.
2Reliability
If traditional CASP encodes reaction rules for maximum reliability, then experimental realization reliability is improved, but step economy and atom economy deteriorate due to inclusion of unnecessary protecting group manipulations and low impact steps
Solution Approach 1:
The patent extracts and removes low-impact steps from traditional CASP-generated routes. By calculating graph edit distances for each step, the system identifies and eliminates unnecessary protecting group manipulations, redox operations, and functional group interconversions that do not contribute significantly to forming target bonds, thereby reducing synthesis time while maintaining reliability of the core high-impact steps.
Solution Approach 2:
The patent applies partial action by focusing computational resources on evaluating only the most impactful steps in the synthesis route. Rather than exhaustively analyzing every reaction step with detailed experimental parameters, the system uses graph edit distances to identify key steps that require optimization, performing excessive analysis only where it matters most for reducing synthesis time.
3Reliability
If automated retrosynthesis focuses on well-precedented reactions, then reaction predictability is improved, but synthesis route complexity increases due to lack of innovative key steps
Solution Approach 1:
The patent inverts the traditional approach by not starting with well-precedented reactions and then trying to connect them, but rather starting with the target molecule structure and working backwards to identify the most efficient disconnections. The graph edit distance methodology enables the system to evaluate multiple disconnection options objectively, selecting those that create the simplest overall route even if they involve less conventional reactions.
Solution Approach 2:
The patent adds a new dimension to synthesis planning by incorporating graph edit distance calculations as an additional evaluation criterion beyond traditional reaction reliability metrics. This dimensional addition allows the system to simultaneously consider both predictability (through reaction knowledge bases) and route simplicity (through graph theory), finding optimal balance points that reduce overall route complexity.
Data Source
AI summary
The present disclosure provides methods, systems, and non-transitory computer-readable media for identifying efficient chemical synthesis processes, using molecular graph editing.