Department of Material Science, Graduate School of Science and Technology, Yamaguchi University, Tokiwadai, Ube, Japan.
Molecules. 2010 Nov 15;15(11):8289-304. doi: 10.3390/molecules15118289.
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(N)Ar 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.
本研究描述了一种使用理论计算（即计算机辅助合成路线开发）开发合成路线的尝试。KOSP 程序为生成 2,6-二甲基色满-4-酮创建了四条潜在的合成路线。然后对这四条合成路线进行了计算机筛选。计算机筛选是指在实际进行实验工作之前对合成路线进行理论分析。Hoddgets 等人已经报道了使用 Mitsunobu 反应的合成路线。在对两个 S(N)Ar 反应和迈克尔反应进行实验检查之前，也进行了理论研究。使用 DFT 计算进行的计算机筛选表明，只有迈克尔反应可能产生目标产物。实验工作证实，使用迈克尔反应可以以 76.4%的产率获得目标产物。除 Mitsunobu 反应外，其他两条路线均未能生成目标产物。我们的结果表明，理论计算可用于在开发新的合成路线时减少需要进行的实验数量。
