Jun Sung Kang, Jin Yi Jung, Chan Jae Cho, Seoungwoo Kang, Yeonjoon Kim, Jae Hyun Kim
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引用次数: 0
摘要
Cynandione A是一种天然联芳基产物,具有双苯乙酮结构,因其具有抗炎、神经保护、抗氧化和增脂等多种生物活性而受到广泛关注。然而,cynandione A有限的天然和商业可用性阻碍了大规模评估,特别是体内研究。在此,我们报告了一锅克级合成cynandione a .该合成的关键步骤是乙酰双酚在苯醌底物上的区域选择性共轭加成,该过程已通过密度泛函理论(DFT)计算进行了机制探索。不同途径过渡态的显著能量差异表明,乙酰双酚亲核试剂的C3位置是唯一的加成位点。经过精心优化,一锅法合成出了克级氰二酮A,收率高。该方法是一种实用的、可扩展的合成氰二酮a的方法,具有良好的锅经济性。
One-Pot Gram-Scale Synthesis of Cynandione A and Detailed Mechanistic Insights into its Regioselectivity.
Cynandione A, a natural biaryl product with a bis-acetophenone structure isolated from Cynanchi wilfordii Radix, has garnered considerable attention because of its diverse biological activities, including anti-inflammatory, neuroprotective, antioxidant, and adipogenic effects. However, the limited natural and commercial availability of cynandione A impedes large-scale evaluations, particularly in vivo studies. Herein, we report a one-pot gram-scale synthesis of cynandione A. The key step of this synthesis is a regioselective conjugate addition of acetyl bisphenol to a benzoquinone substrate, which has been mechanistically explored using density functional theory (DFT) calculations. The significant energetic differences at the transition states among the possible pathways indicate the C3 position of the acetyl bisphenol nucleophile as the exclusive site of addition. Through careful optimization, the one-pot synthesis affords cynandione A in a gram scale with a high yield. This method presents a practical, and scalable approach for synthesizing cynandione A with excellent pot economy.
期刊介绍:
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