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James Law1, Anthony Cook2, Orr Ravitz1, A. Peter Johnson2 and Aniko Simon1
1 SimBioSys Inc., Toronto, Canada
2 School of Chemistry, University
of Leeds, Leeds, UK
view: Abstract;
Presentation
Abstract:
The concept of computer aided synthesis design
(CASD) emerged in the late 1960’s as a result of the rise of digital
computing, as well as the introduction of the paradigm of
retrosynthetic analysis by EJ Corey. The field was accepted initially
with enthusiasm, but eventually faced high levels of skepticism from
chemists, leading to its decline in the 1990’s. The main reason for the
rejection of CASD was the difficulty in capturing broad enough chemical
space, and in keeping the systems abreast with advances in organic
synthetic methods. The contemporary retrosynthetic analysis software,
ARChem, overcomes these
barriers by employing a combination of automated rule generation with
manual rule curation to achieve a comprehensive coverage of the
chemical reactions space at an adequate level of accuracy. We discuss
the algorithmic approach for rule-generation from large databases of
reactions such as Reaxys and ChemInform, and the instances in which
manual editing of rules is critical. We provide examples to illustrate
the rule extraction and rule curation
processes, and demonstrate the utility of the system in the design of synthetic routes for targets of pharmaceutical importance.
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