Chemical synthesis analysis program


The computer program LHASA, which has been under continuous development at Harvard and various collaborating universities for more than 25 years, is intended to assist organic chemists in designing multistep routes to complex molecules. The program accepts as input a target molecule drawn in the language of structural formulae that is common to all organic chemists. A perception of the target is conducted to identify molecular features that influence the development of retrosynthetic routes (e.g. functional groups, stereocenters, rings, etc.) The user is then prompted to specify a strategy and substrategy, or tactic, to guide the retrosynthetic analysis. Finally, the program selects retroreactions ("transforms") from its chemical knowledge base in accordance with the processing tactic and applies these transforms to generate retrosynthetic precursors which are structurally simpler than the target. The user selects one of the precursors for further processing, and the analysis proceeds in an interactive fashion until readily available hypothetical starting materials are obtained.

Interaction with the program is entirely graphical, allowing chemists with little or no computer experience to use the program effectively. Considerable effort has been expended to enhance the user-friendliness of the program. New features include on-line setup menus for modifying run-time parameters, graphical display of perception information, algorithms for automated selection of strategies and tactics, and on-line explanations of button functions.

Intellectual Property Status: Patent(s) Pending


When planning a laboratory synthesis, the expert organic chemist does not simply apply every reaction that might be used to make the target structure and all intermediate structures. Rather, s/he identifies one or more strategies and tactics to guide the analysis in the direction of maximal retrosynthetic simplification of the target. In a similar fashion, LHASA (an acronym for Logic and Heuristics Applied to Synthetic Analysis) uses strategies and tactics to emulate the chemists' reasoning and limit the scope of the search for transforms. There are five major strategies in LHASA: functional-group and pattern-based, topological or "strategic bond", key-transform, stereochemical, and starting-material-oriented. To assist the chemist in selecting strategies, a "LHASA Suggestions" mode has recently been implemented in which the program suggests tactics based on its perception of synthetically-significant structural features.