Progress in the Synthesis of Oxindole‐Naphthoquinone Molecular Hybrid Scaffolds: A Concise Review

Abstract

Oxindole and 1,4-Naphthoquinone both are the versatile heterocyclic scaffolds which not only found in many naturally occurring and pharmaceutically imperative compounds but also have explored as an important precursor in the synthesis of a library of structurally diverse molecular frameworks desirable for biological studies. For a few decades, significant emphasis is given on the synthesis of both of these important privileged scaffolds to accomplish promising new heterocycles with chemical and biomedical relevance. Due to such prevalence and prominence of oxindole and 1,4-naphthoquinone frameworks in medicinal and synthetic chemistry, many researchers have taken efforts to synthesize the oxindolenaphthoquinone molecular hybrid in a single nucleolus. These efforts have led to the development of different approaches and green technologies in recent years, which includes nano catalysts, microwaves and, ultrasound irradiation. In this review, we have focused our attention, specifically, to provide insight into the modern approaches to the synthesis of oxindole-1,4naphthoquinone molecular hybrid and technical advances in this research field till April 2020. The review is mainly made up of four main parts which contain 2-component, 3-component, 4-component, and other multistep miscellaneous approaches utilized to synthesize this oxindole-1,4-naphthoquinone molecular hybrid. These four main parts are also subdivided according to different substituents present on oxindole-1,4naphthoquinone molecular hybrid. This review focused specifically on the collection of literature on the reaction of isatin with 2-hydroxyl-1,4-naphthoquinone(Lawsone) to afford oxindole-1,4-naphthoquinone molecular hybrid.

Recent Advances in the Synthesis of 2-Hydroxy-1,4-naphthoquinone (Lawsone) Derivatives

“…These reactive intermediates are subsequently captured by 2-hydroxy-1,4-naphthoquinone, resulting in the formation of one new C-C bond and two new C-N bonds (Scheme 47). 76 Scheme 47 2,3-Fused pyrrole derivatives 144a-h. [4,5]thiazolo[2,3-b]quinazolin-14-ium hydroxide derivatives 157a-g. These derivatives were synthesized through a one-pot, three-component reaction involving aryl glyoxal monohydrates 155a-g, 2-hydroxy-1,4-naphthoquinone 1, and either 2-aminothiazole 156.…”

“…Moreover, the starting materials and catalysts used in the reaction are readily accessible, contributing to the convenience and accessibility of the method. 78 Scheme 50 Benzo[g]thiazolo[2,3-b]quinazolin-4-ium and Benzo[g]benzo [4,5] thiazolo [2,3-b]quinazolin-14-ium hydroxide derivatives 157a-g.…”

“…[1][2][3] It is one of the simplest naturally occurring naphthoquinones and is primarily known for its presence in the leaves of the henna plant (Lawsonia inermis), where it imparts a red-orange dye. 4 Humans have utilized henna extracts containing lawsone for thousands of years as hair and skin dyes, highlighting its historical and cultural significance. 5,6 Beyond its dyeing properties, 2-hydroxy-1,4-naphthoquinone exhibits a range of biological activities, including antibacterial, antifungal, anti-inflammatory, antiviral, and antineoplastic properties.…”

Discovery of Novel Naphthoquinone–Chalcone Hybrids as Potent FGFR1 Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modeling

“…The pharmacological significance of chalcone and naphthoquinone scaffolds has inspired the scientific community to synthesize hybrid molecules based on these skeletons to provide diverse biological activities. − The hybridization of these moieties (chalcone and naphthoquinone) into a single molecule has been reported in the literature. − For example, chalcone–naphthoquinone hybrids I – III (Figure ) possessing anticancer activity have been studied. − The anthraquinone-based chalcone I showed potent activity against HeLa, LS174, and A549 cancer cell lines (IC 50 = 1.93–17.18 μM) and exhibited strong antiangiogenic activity . Shikonin-based chalcone II showed potent anticancer and antitubulin effects against HeLa, MCF-7, and A549 cancer cell lines (IC 50 = 2.36–5.84 μM) .…”

Unprecedented, catalyst‐free, and rapid one‐pot, three‐component green synthesis of substituted 3‐hydroxy‐2‐oxindoles in water

“…In continuation of our interest in the development of novel and eco‐friendly protocols [25–32], we developed an unprecedented, catalyst‐free method for the synthesis of substituted 3‐hydroxy‐3‐(3‐hydroxy‐5‐methyl‐1 H ‐pyrazol‐4‐yl)indolin‐2‐one. Among many approaches that have been published to synthesize a variety of 3‐hydroxy‐2‐oxindoles, our method holds a special tag of a new route.…”