Structural and Computational Investigation of Intramolecular N···H Interactions in α‐ and β‐Fluorinated 7‐Azaindoline Amides
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- Lennart Brewitz
- Institute of Microbial Chemistry (BIKAKEN) Tokyo Kamiosaki 3‐14‐23 141‐0021 Shinagawa‐ku, Tokyo Japan
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- Hidetoshi Noda
- Institute of Microbial Chemistry (BIKAKEN) Tokyo Kamiosaki 3‐14‐23 141‐0021 Shinagawa‐ku, Tokyo Japan
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- Naoya Kumagai
- Institute of Microbial Chemistry (BIKAKEN) Tokyo Kamiosaki 3‐14‐23 141‐0021 Shinagawa‐ku, Tokyo Japan
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- Masakatsu Shibasaki
- Institute of Microbial Chemistry (BIKAKEN) Tokyo Kamiosaki 3‐14‐23 141‐0021 Shinagawa‐ku, Tokyo Japan
説明
<jats:p>Novel fluorinated <jats:italic>N</jats:italic><jats:sup>1</jats:sup>‐acylated 7‐azaindolines have been synthesized and their conformations analyzed by X‐ray diffraction and NMR spectroscopy: Unusual intramolecular interactions between the 7‐nitrogen and amide α‐hydrogen atoms were identified. The strength of these interactions correlate with the electron‐withdrawing character of the amide α substituents. A combination of experimental and computational approaches revealed a significant substituent effect when the substituent (H, OMe, F, CN) at the 4‐position of the 7‐azaindoline scaffold was varied. As these intramolecular interactions also occur in non‐fluorinated <jats:italic>N</jats:italic><jats:sup>1</jats:sup>‐acylated 7‐azaindolines and similar heterocycles, this study is relevant to medicinal chemistry: The results will facilitate the prediction of the predominant conformations of <jats:italic>N</jats:italic><jats:sup>1</jats:sup>‐acylated‐7‐azaindoline‐containing bioactive molecules and thus potentially contribute to drug discovery programs.</jats:p>
収録刊行物
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- European Journal of Organic Chemistry
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European Journal of Organic Chemistry 2018 (6), 714-722, 2017-11-20
Wiley
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詳細情報 詳細情報について
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- CRID
- 1360848655033132672
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- ISSN
- 10990690
- 1434193X
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- データソース種別
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- Crossref
- KAKEN