One of the aspects of maturation is the transition from the egocentric viewpoint to a phase where one engages and considers others. It is true for kids that begin to understand and cope with social situations. It is true for soccer players, or scientists for that matter, that understand that it is not all about personal skills and knowledge, but it is also about how you utilize those in the team play. And it is true for software applications that shift from the stage of proving their algorithms’ capabilities, to become integrable with other applications and merge into a workflow that creates real value for the user.
Since the previous release, work has continued on improving reaction rules generation in ARChem as well as the retrosynthetic search. Significant progress has been made in detecting and highlighting potential functional groups interference. The chemoselectivity issue is a challenge that requires a combination of data mining, profound chemical perception, and supplemental expert knowledge-bases. Another area that recorded a significant improvement is scoring. The retrosynthetic search commonly generates a vast solutions-space with hundreds, and possibly thousands of paths. Navigating systematically through all the options is typically too time consuming, and scoring becomes pivotal in prioritizing the solutions for the user to inspect. Scoring now better reflects a chemist’s assessment regarding the feasibility of a synthetic route. It accounts for synthetic depth, reliability of individual reaction steps, yield, wastage, chemical interference and other considerations in a successful balance.
Alongside the major improvements in the underlying technology, the focus of the last few months has been on usability and integrability:
Reaction examples are directly linked to the Reaxys records for full data and literature access.
Starting materials arrived at during the search are pointing to the corresponding records in online chemical vendors catalogues.
Costs of starting materials are displayed, and route cost is evaluated.
As a rule is being used in the analysis, the example reactions that were used to generate this rule are now ordered by relevance to the synthetic route.
The solutions space can be pruned using user-defined filters.
Changes to the GUI make solutions navigation more efficient, and the general look and feel of the system is more polished and refined.
Here is an example that demonstrates some of the features mentioned above, and also elegantly validates the concept of automated retrosynthetic chemistry. The suggested route was ranked number 1 by the system. It manifests a sequence of three reaction rules that simplify the target all the way to commercially available starting materials, shown with their associated prices per mole. In this particular case, all the suggested transforms were actually exactly found in the set of reactions that generated the respective rules during the automated process of retrosynthetic-rule extraction. All the examples, and the exact-matches can be accessed via the links provided along the retrosynthetic tree. At the bottom right we show a literature reference for a synthesis of the molecule validating the route. ARChem offers a set of 28 distinct solutions that constitute a gateway to a much larger solutions space that can be accessed through the “n of m transforms” links. The user can build different solutions by selecting any of the suggested alternative transforms.
ARChem has made a long way from its proof of concept days. It is now maturing into a tool that can offer real benefits to the medicinal or process chemist, not the least thanks to the continuous feedback that we get from users. In the next few months substantial changes are anticipated in all the aspects of the system. Maturity does not mean stagnation – ARChem is at the forefront of the field of computer aided synthesis design, and intensive R&D guarantees that major advances are still to come. Stay tuned.
posted by Orr