Towards the Development of Synthetic Routes Using Theoretical Calculations An Application of In Silico Screening to 2,6-Dimethylchroman-4-one 英文参考文献.docVIP

Molecules 2010, 15, 8289-8304; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Towards the Development of Synthetic Routes Using Theoretical Calculations: An Application of In Silico Screening to 2,6-Dimethylchroman-4-one Kenji Hori 1,*, Hirotaka Sadatomi 2, Atsuo Miyamoto 3, Takaaki Kuroda 2, Michinori Sumimoto 1 and Hidetoshi Yamamoto 1 1 Department of Material Science, Graduate School of Science and Technology, Yamaguchi University, Tokiwadai, Ube 755-8611, Japan 2 Transition State Technology, Tokiwadai, Ube 755-8611, Japan; E-Mail: sadatomi@tstcl.jp (H.S.) 3 NARD Institute, Ltd., Nishinagasu, Amagasaki 660-8050, Japan; E-Mail: miyamoto@nard.co.jp (A.M.) * Author to whom correspondence should be addressed; E-Mail: kenji@yamaguchi-u.ac.jp; Tel.: +81-836-85-9238; Fax: +81-836-85-9601. Received: 17 September 2010; in revised form: 9 November 2010 / Accepted: 11 November 2010 / Published: 15 November 2010 Abstract: 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 SNAr 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.