A large number of convincing evidences has revealed the correlation of the pathogeny of diseases with the oxidative damages of DNA, protein, biomembrane, and other biological species, while supplementation of antioxidants is demonstrated to be a promising way to avoid, at least, rectify the unbalance redox status in vivo. Although many endeavors have focused on synthesis of antioxidants, a main hurdle still hinders the wide usages of synthetic antioxidants because of low bioavailability and potential cytotoxicity. The search for antioxidants with multiple functional groups being recognized by different receptors becomes a much sought by researchers, and multicomponent reactions (MCRs) provide with powerful tools for the construction of multifunctional antioxidants. Presented herein is a personal account on the application of MCRs for the synthesis of multifunctional antioxidants, while radical‐induced oxidation of DNA acts as the experimental system for evaluating antioxidative effect. Concretely, the Biginelli three‐component reaction (3CR) affords such a dihydropyrimidine scaffold that the tautomerization between C=S and C−SH leads to antioxidative effect. The Povarov 3CR is able to integrate multiple antioxidative groups, i. e., ferrocenyl and −N(CH₃)₂, into a quinoline scaffold, while the Groebke 3CR provides with imidazo[1,2‐a]pyridine skeleton for inhibiting DNA oxidation. Additionally, the Knoevenagel‐related MCRs also become efficient strategies for achieving radical‐scavengers. On the other hand, the Ugi 4CR and Passerini 3CR result in the dipeptide and α‐acyloxycarboxamide, respectively, with the benefit for the integration of antioxidative features by aliphatic chains. Therefore, MCRs have emerged as efficient tools for integrating multiple antioxidative features into one molecule in order to meet with complicated requirements from various biological surroundings.

中文翻译：

---

用于将多个官能团整合到抗氧化剂中的多组分反应

大量令人信服的证据表明，疾病的致病性与DNA，蛋白质，生物膜和其他生物物种的氧化损伤之间存在相关性，而补充抗氧化剂被证明是避免至少纠正这种疾病的一种有希望的方法。体内不平衡氧化还原状态。尽管许多努力集中在抗氧化剂的合成上，但是由于生物利用度低和潜在的细胞毒性，主要障碍仍然阻碍了合成抗氧化剂的广泛使用。寻找具有被不同受体识别的多个功能基团的抗氧化剂成为研究人员的迫切需求，而多组分反应（MCR）提供了构建多功能抗氧化剂的强大工具。本文介绍了MCR在多功能抗氧化剂合成中的应用，而自由基诱导的DNA氧化则是评估抗氧化作用的实验系统。具体而言，Biginelli三组分反应（3CR）提供了这样的二氢嘧啶骨架，使得C = S和C-SH之间的互变异构导致抗氧化作用。一世。例如，二茂铁基和-N（CH ₃）₂进入喹啉骨架，而Groebke 3CR提供了咪唑并[1,2- a ]吡啶骨架来抑制DNA氧化。此外，与Knoevenagel相关的MCR也成为实现激进清除剂的有效策略。另一方面，Ugi 4CR和Passerini 3CR分别产生二肽和α-酰氧基羧酰胺，有利于脂族链整合抗氧化功能。因此，MCR已经成为将多种抗氧化特征整合到一个分子中的有效工具，以满足各种生物环境的复杂要求。