| Autor: |
Funaki K; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan., Tabata H; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan., Nakazato Y; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan., Takahashi Y; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan., Tasaka T; Affinity Science Corporation, 1-11-1 Nishi-Gotanda, Shinagawa-ku, Tokyo 141-0031, Japan., Takahashi H; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan., Natsugari H; Affinity Science Corporation, 1-11-1 Nishi-Gotanda, Shinagawa-ku, Tokyo 141-0031, Japan.; Faculty of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan., Oshitari T; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. |
| Abstrakt: |
5 N -Acylation of 1 N -methyl-1,5-benzodiazepin-2-ones with ( S )-2-phenylpropanoyl and ( S )-2-phenylbutanoyl chlorides afforded the (a 1 S ,a 2 S , S )-atropisomer ( I ) diastereoselectively over the (a 1 R ,a 2 R , S )-isomer ( II ) in the ratio of 1:0.06-0.15. The preferential formation of I may be explained by the thermodynamically preferable π-π stacking interaction between two benzene rings in the benzodiazepine ring and the acyl chloride during the reaction. Analysis using ab initio calculations (RI-MP2/6-31+G(d) level of theory) for the acylation reaction indicated the π-π stacking interaction in the transition state. Furthermore, isomer I was shown to be thermodynamically more stable than II . The higher stability of I may be caused by the folded form of the two benzene rings, which was revealed by NMR, X-ray, and computational analyses. |
