Abstract

Medicinal chemistry of heterocycles especially β-lactams have been an important discovery in today’s mankind. β-Lactam nucleus is structural feature and core of the biological activity of one of most successful classes of therapeutics to date characterized by a broad spectrum of activity and low toxicity. It constitutes classes of drugs that includes the antibiotics like penicillins, cephalosporins, clavulanic acid, monobactams and also shows wide range of important biological activities such as anti-cancer, anti-inflammatory and anti-malarial. The monocyclic β-lactams and their hetero-substituted conjugates are also applied for the synthesis of many classes of compounds which include taxol derivatives, alkaloids and amino acids. Antimicrobial resistance is one of the major and growing concerns in hospital and community acquired infections and new anti-microbial agents are therefore urgently required. So now, the organic chemists have focussed on the modification of existing molecules for the synthesis of new compounds having diverse pharmacological activities with broad spectrum activity. Monocyclic β-lactams are stable to hydrolysis by β-lactamases in comparison to other β-lactams and thus are attractive platform for searching anti-bacterial agents. The discovery of differently substituted 3-alkyl/aryl β-lactams having significant anti-microbial activities have given insight that substitution at C-3 and C-4 of β-lactam ring affects the biological activity of the ring. So, keeping this in mind and synthetic utility of β-lactams here we have made an attempt towards the feasibility and efficiency of 3-(p-substituted-phenylthio)-β-lactams towards Lewis acid functionalization reactions. In our previous works, we have explored the synthetic utility of cis-3-chloro-3-phenyl/benzyl/methylthio-β-lactams as suitable substrate for the Lewis acid catalysed nucleophilic substitution. The current work is designed to explore the effect of electronic changes at phenylthio group at C-3 on the products profile in the Lewis acid catalysed nucleophilic substitution reactions.

Graphic abstract

The synthetic utility 3-(4′-substitutedphenylthio)-azetidin-2-ones towards Lewis acid catalyzed C-3 functionalization reactions have been studied.

中文翻译：

---

3-（4'-取代苯硫基）-氮杂环丁烷-2-酮的合成及路易斯酸催化功能化的研究

摘要

杂环，尤其是β-内酰胺类的药物化学在当今人类中是重要的发现。β-内酰胺核是迄今为止最成功的治疗药物之一的结构特征和生物学活性的核心，其特征在于活性广谱且毒性低。它构成的药物类别包括青霉素，头孢菌素，克拉维酸，单bactams等抗生素，并且还显示出广泛的重要生物活性，例如抗癌，抗炎和抗疟疾。单环β-内酰胺及其杂取代的共轭物也可用于合成许多类化合物，包括紫杉醇衍生物，生物碱和氨基酸。在医院和社区获得性感染中，抗菌素耐药性是主要且日益关注的问题之一，因此迫切需要新的抗菌剂。因此，现在，有机化学家将注意力集中在现有分子的修饰上，以合成具有多种药理活性和广谱活性的新化合物。与其他β-内酰胺相比，单环β-内酰胺对β-内酰胺酶的水解稳定，因此是寻找抗菌剂的诱人平台。具有显着抗微生物活性的不同取代的3-烷基/芳基β-内酰胺的发现使人认识到，β-内酰胺环在C-3和C-4处的取代会影响该环的生物活性。所以，对-取代的苯硫基）-β-内酰胺对路易斯酸官能化反应的反应。在我们以前的工作中，我们探索了顺式-3-氯-3-苯基/苄基/甲硫基-β-内酰胺的合成实用性，作为路易斯酸催化亲核取代反应的合适底物。当前的工作旨在探讨在路易斯酸催化的亲核取代反应中，C-3上苯硫基电子变化对产物谱的影响。

图形摘要

已经研究了合成的3-（4'-取代的苯硫基）-氮杂环丁烷-2-酮对路易斯酸催化的C-3官能化反应的作用。