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アスコルビレイテッド・ディターペノイド・ホンコノイド A-D の構造解明とバイオインスピレーションによる総合成
Jin-Xin Zhao1, Yan-Yan Yu1,2, Sha-Sha Wang1
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.
Journal of the American Chemical Society
|February 3, 2018
まとめ
研究者はDysoxylum hongkongenseから新しいアスコルビラテテルペノイド,Hongkonoids A-Dを分離しました. 全合成により,それらの構造が確認され,一部の化合物はNF-κBおよび11β-HSD1に対する抑制作用を示した.
科学分野:
- 自然製品化学
- 有機合成
- 薬剤化学
背景:
- ダイソキシラム・ホンコングンセスは 複雑な天然製品の植物源です
- アスコルバイレートテルペノイドは 独特の化学構造のクラスです
- トリサイクルのスピロケタルブチロラクトン分子はテルペノイドでは稀である.
研究 の 目的:
- ダイソキシラム・ホンコングンセスの新しい化合物を分離し特徴づけること
- ホンコノイド A-Dの構造を解明する
- ホンコノイドADを合成し 生物学的活動を評価する
主な方法:
- 自然製品の分離と浄化は,光譜データ (NMR,MS) を使用する.
- X線結晶学,CD分析,化学分解による構造解明
- バイオインスピレーションによるワンポットカスケード反応とNHKカップリングを含むコンバージェント戦略を用いた総合成.
主要な成果:
- 4つの新しいアスコルビレートされたテルペノイド,Hongkonoids A-D (1-4) が分離されました.
- 独特の5,5,5結合の三循環性スピロケタルブチロラクトン部分とディターペノイドの長鎖が特徴付けられました.
- 全体合成は12〜14段階で,総収量5.4〜9.6%で達成される.
- 化合物はNF-κB,11β-HSD1,およびステロール合成に対する抑制作用を示した.
- 化合物34は,LPS誘発の炎症反応の有意な抑制を示した.
結論:
- Hongkonoids A-Dは,ユニークな構造の枠組みを持つ新しいテルペノイドです.
- 総合成は提案された構造を検証し,これらの化合物へのアクセスを提供します.
- 単離された化合物と合成アナログは,特にNF-κB阻害体として有望な生物学的活性を示しています.
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