A paper on our joint research project with Yamaguchi University, titled “A method to search the most stable reaction pathway and its application to the Pinner Pyrimidine Synthesis reaction,” has been published.

　The development of synthetic routes for functional chemicals has historically relied heavily on the experience and intuition of organic synthetic chemists. When the structure of the target molecule is complex, numerous synthetic routes exist, making it difficult to determine which route to adopt. To reduce the number of synthetic routes used in experiments, we introduced “in silico screening.” This requires searching for transition states (TS) in the synthetic route, and we proposed a method to derive new TS structures for the target reaction using TS structures contained in a TS database (TSDB).
　However, this method rarely yields the most stable TS structure among the possible conformations. In other words, the stability of the transition state (TS), reactants, and products largely depends on the initial structure used for optimization. Therefore, this method may lack sufficient data when comparing calculated values ​​with experimental values. To solve this, it is necessary to find the reaction mechanism that includes the most stable TS and the molecules involved in the reaction. In this paper, we propose a method for searching for the most stable reaction pathway and apply it to the Pinner pyrimidine reaction between ethyl 3-oxobutanoate and 3-ethoxypropanimidamide.

• Maeyama, E.; Yamaguchi, T.; Sumimoto, M.; Hori, K. A Method to Search the Most Stable Reaction Pathway and Its Application to the Pinner Pyrimidine Synthesis Reaction. J. Comput. Aided Chem. 2021, 22 (0), 1–7. DOI: 10.2751/jcac.22.1