Towards the Development of Synthetic Routes Using Theoretical Calculations: An Application of In Silico Screening to 2,6-Dimethylchroman-4-one

Molecules

Kenji Hori¹  Hirotaka Sadatomi¹  Atsuo Miyamoto¹  Takaaki Kuroda¹  Michinori Sumimoto¹ 

[1] ¹Department of Material Science, Graduate School of Science and Technology, Yamaguchi University, Tokiwadai, Ube 755-8611, Japan ²Transition State Technology, Tokiwadai, Ube 755-8611, Japan ³NARD Institute, Ltd., Nishinagasu, Amagasaki 660-8050, Japan

关键词: In silico screening;    synthetic route development;    theoretical calculations;    Mitsunobu reaction;    Michael reaction;   

DOI  :  10.3390/molecules15118289

来源: mdpi

【 摘 要 】

This study describes an attempt to develop a synthetic route using theoretical calculations, i.e., in silico synthesis route development. The KOSP program created four potential synthetic routes for generating 2,6-dimethylchroman-4-one. In silico screening of these four synthetic routes was then performed. In silico screening involves theoretical analysis of synthetic routes prior to actual experimental work. A synthetic route using the Mitsunobu reaction had already been reported by Hoddgets et al. Theoretical investigations were also conducted on two S_NAr reactions as well as a Michael reaction before they were examined experimentally. In silico screening using DFT calculations indicated that only the Michael reaction was likely to produce the target. Experimental work confirmed that the target was obtained in a yield of 76.4% using the Michael reaction. The other two routes, except for the Mitsunobu reaction, failed to generate the target. Our results demonstrate that theoretical calculations can be used to narrow down the number of experiments that need to be conducted when developing novel synthetic routes.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.