ベルグマンサイクライゼーションの電子制御:ビニール置換の顕著な役割
1Contribution from the Bioorganic, Medicinal Chemistry, and Molecular Engineering Laboratories, Department of Chemistry, Northeastern University, 360 Huntington Ave., Boston, Massachusetts 02115, USA.
Journal of the American Chemical Society
|July 18, 2001
まとめ
ビニルの置換は,エネダイヌスのベルグマンサイクルに大きく影響する. 電子を取り除くグループは,サイクライゼーションバリアを上昇させ,電子を寄付するグループは,それを低下させ,薬物設計の洞察を提供します.
科学分野:
- コンピューティング・ケミストリー
- 有機化学 オーガニック・ケミストリー
- 薬用化学 薬用化学について
背景:
- 3-エネ-1,5-ダイヌのベルグマンサイクル化は,有機合成における重要な反応である.
- このサイクロアロマチゼーションに対する置換剤の効果を理解することは,反応性を制御するために極めて重要です.
- 以前の研究では,ベルグマン・サイクライゼーションに影響を与える様々な要因を調査した.
研究 の 目的:
- ヴィニル置換が,3-エネ-1,5-ダイヌースのベルグマンサイクル化に及ぼす影響を調査する.
- 電子提供群と電子取り除く群がサイクライゼーションバリアにどのように影響するかを分析する.
- 反応に対する無効化と異異芳香系の影響を調査する.
主な方法:
- 密度関数理論 (DFT),特にBLYP関数を用いた初期計算研究.
- 鍵となる化合物のブリュックナー軌道計算のより高いレベル.
- 46のエネダイン,44の移行状態,そして67のp-ベンジン中間物質の体系的な調査.
主要な成果:
- 電子を取り除くグループはサイクライゼーションバリアを増加させ,シグマドナーグループはそれを減少させる.
- Pi結合は,サイクライゼーションバリアに最小限の影響を及ぼします.
- 解消は,一般に,より小さなまたは充電されたリングがより大きな効果を示し,バリアを低くまたはわずかに上げます.
- p-ベンジンの中間物質の可逆性または前向き反応性は,表面的な速度阻害を説明することができます.
- いくつかのヘテロアロマティック系において予期せぬ行動が予測される.
結論:
- ビニールの置換と電子効果は,ベルグマンサイクリングの速度を大幅に調節します.
- これらの効果を理解することは,新しいエネディイン前薬候補剤を設計するための基礎を提供します.
- 計算による洞察は,標的の生物学的応用のための分子の開発を導く.
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