Mini-Reviews in Organic Chemistry - Volume 18, Issue 1, 2021

Linoleic Acid (LA) (omega-6) and Alpha-Linolenic Acid (ALA) (omega-3) are essential fatty acids and give rise to Arachidonic Acid (AA), Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) that are important in metabolic homeostasis. The omega-6:omega-3 ratio can be a prognostic consideration in cardiovascular and inflammatory diseases. Sphingolipids are bioactive lipids found in cell membranes that play a role in cell growth, differentiation and apoptosis. Electrospray Ionization (ESI) coupled with tandem Mass Spectrometry (MS/MS) is a simple and speedy method to identify and quantify these lipids in various biological matrices. Tandem mass spectrometric analyses can be performed on cell lysates, tissue homogenates and serum samples to measure quantitative changes directly in lipid extracts from these different matrices. The present review summarizes measurement of omega-3 (n-3) and omega-6 (n-6) Polyunsaturated Fatty Acids (PUFAs), their metabolism to eicosanoids and their role in certain disease states. Altered sphingolipid metabolism is also associated with a number of human diseases. Therefore, understanding sphingolipid metabolism is important to comprehend the function of sphingolipids in cellular processes. In this review, we focus on pathways of Ceramide (CER) and Sphingomyelin (SM) synthesis and discuss altered levels reported in disease states. Results of reported studies herein clearly show that PUFAs, SMs and CERs carry out a large number of fundamental functions. They serve as structural elements in cellular membranes, and they work as signaling molecules. Alterations in their amounts of expression occurring in diabetes, obesity, inflammation and ER stress-related conditions lead to dysfunctions contributing to disease pathogenesis.

Magnetic nanoparticles have gained a great deal of attention from both academic and industrial point of view, owing to their unique properties including high surface area, and superparamagnetism, which enable them to be suitable for modification with many compounds and employing them as a catalyst in organic reactions. In this mini-review, we have summarized the application of surface-modified magnetite nanoparticles as magnetically recoverable catalysts in heterocyclic synthesis. These catalysts include silica, biopolymer, acid, amine, transition metal, ionic liquid and metal organic framework supported magnetite catalysts.

The functionalization of the skeletal systems of heterocycles represents a significant goal for the development of new compounds. The heterocyclic molecule xanthine (3,7-dihydro-1Hpurine- 2,6-dione) is a purine base with a bicyclic ring skeleton and four different nitrogen atoms, three of them are -NH groups. The principal derivatives are the well known natural methylxanthines (e.g., caffeine, theophylline and theobromine) that have prominent physiological effects at a very low dose. The natural methylated xanthines, theophylline, theobromine and caffeine, are present in different plants such as the tea, cocoa and coffee species. For this reason natural xanthines can be considered as bio-based and renewable starting materials; their use in organic synthesis is strongly recommended in order to carry out sustainable chemistry. Essentially, the xanthine scaffold led to the preparation of numerous compounds very attractive in the pharmaceutical field, and these drugs are commercialized for a wide range of biological activities. The scope of this mini-review is to consider the use of natural xanthines as starting material in chemical transformations carried out in organic solvents, without the intent to be exhaustive of all the synthetically chemical applications. More information on the chemical and electrochemical reactivity of this structural core in an organic solvent can be useful for the scientific community. The effectiveness of natural xanthines can be improved by modifying the structures of these already biologically active compounds.

There are four types of pyridopyrimidines namely pyrido[2,3-d], pyrido[3,4-d], pyrido[ 4,3-d]pyrimidines, and pyrido[3,2-d]pyrimidines. Different methods of preparation of pyrido[2,3- d]pyrimidines are summarized. Synthesis of pyrido[2,3-d]pyrimidines can be from pyrimidines derivatives or pyridine derivatives. We can start from pyrimidine derivatives and build a pyridine ring. 5,7-Diphenylpyrido[2,3-d]pyrimidines 3 and 4 were obtained by the reaction of 6-aminouracil (1) with α,β-unsaturated ketone. 6-Amino-1,3-dimethyluracil 10 was reacted with an equimolar amount of Mannich bases 11a-c under an atmosphere of nitrogen to give pyridopyrimidines 14a-c via the formation of the intermediates 12a-c & 13a-c. 4-Benzylamino derivative 19 could be converted to pyrido[2,3-d]pyrimidine derivative 20 by the reaction with dimethylformamide/ dimethylacetal. In the same way, we can start from pyridine derivatives and build a pyrimidine ring. Different reported biological activities of pyrido[2,3-d]pyrimidines are discussed e.g. selective adenosine kinase inhibitors, analgesic, anti-inflammatory, antimicrobial and herbicides, selective inhibitor of the tyrosine kinase activities of the Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors.

In this review article, we describe the application, reactivity and synthesis of isoxazole derivatives, more specifically, the application, reactivity, and synthesis of 3,5-disubstituted, 3,4- disubstituted, and 3,4,5-trisubstituted isoxazole using the green method. We review the application of isoxazole in material science, agriculture and pharmaceutical. In material science, isoxazole is used as a photochromic, electrochemical probe for Cu²⁺ and, given its optical properties, in dye-sensitized solar cells, high energy material and liquid crystal. In agriculture, isoxazole is used as an insecticide for managing Callosobruchus chinensis, Acaricidal activity against T. cinnabarinus, and herbicidal activities of 2-cyanoacrylates containing isoxazole. In pharmaceutical, isoxazole shows anticancer, antituberculosis, anti-inflammatory, and acetylcholinesterase inhibitors. Further, we describe various reactions of isoxazole such as ring opens, bromination and iodination, thioynol ethers, intramolecular SEAr reaction, arylation, cycloaddition and photocycloaddition, photoisomerization, Domino transformation of isoxazoles to 2,4-dicarbonyl pyrroles and rearrangement. We also describe the synthesis of 3,5-disubstituted, 3,4-disubstituted and 3,4,5-trisubstituted isoxazole using different methods.

Nowadays, carbon-based nanostructure materials are regarded as promising carriers for drug delivery to improve the effective treatment of diseases. The formation of covalent and noncovalent molecular bonds can be used for surface modification of nano-carriers in order to manipulate their toxicity, water solubility, and cellular internalization. Graphene and its derivatives have shown important potential in drug delivery systems. Among different graphene derivatives, Graphene Oxide (GO) is the most extensively used derivative. GO sheets have possessed certain oxygen functional groups including carboxylic acid groups at the edges, epoxy and hydroxyl groups on the basal planes. The oxygen groups on the surface of GO sheets enhance their capabilities for functionalization with chemical and bioactive molecules. In this review, we highlight the recent researches about the effect of reactive sites on the surface of GO and its derivatives in drug delivery systems. Therefore, the application of GO and its derivatives have been discussed as a delivery system in cancer treatment, gene therapy, and combination therapy, followed by discussions on their related issues. Finally, the review will provide a future perspective to the applications of GO-based materials as part of drug delivery systems, and may open up new viewpoints to motivate broader interests across these interdisciplinary fields.

The heterocyclic compounds are the building blocks for the synthesis of the different biologically active compounds in the organic chemistry. Heterocyclic compounds have versatile synthetic applicability and biological activity. Pyrazole carboxylic acid derivatives are significant scaffold structures in heterocyclic compounds due to biologic activities such as antimicrobial, anticancer, inflammatory, antidepressant, antifungal anti-tubercular and antiviral, etc. The aim of this mini-review is an overview synthesis of pyrazole carboxylic acid derivatives and their biologic applications. The summarized literature survey presents biological activities of pyrazole carboxylic acid derivatives and their various synthetic methods in detail. This mini-review can be a guide to many scientists in medicinal chemistry.

Thiophene derivatives are aromatic five-membered ring compounds made up of one sulfur as heteroatom. These compounds are present in a large number of natural and unnatural compounds with valuable bioactivities. Many of them have a wide range of applications in medicinal chemistry such as antimicrobial, anticancer, antiparasitic, anti-inflammatory, and antihypertensive activities. Some of them are famous drugs in the market nowadays such as Cefoxitin, Cephalothin, Cephaloridine, Temocillin, tinoridine, tiaprofenic acid, tenoxicam, suproprofen and Raltitrexed. The use of thiophene derivatives has also been found in other fields. The application of thiophenes in organic materials thanks to their electronic properties has been reported. In organic synthesis, thiophenes have also drawn the attention of chemists because of their values as intermediates. The employment of thiophene derivatives in agrochemicals, flavors, and dyes has also been found. Due to diverse applications, the synthesis of thiophene derivatives has attracted a lot of attention. Numerous known synthetic methods such as Gewald and Fiesselmann methods have been modified and improved. Furthermore, a large number of novel synthetic approaches to the synthesis of thiophenes have been developed. This review will focus on considerable studies on the synthesis of thiophenes which date back from 2012. In this review, we discussed recent achievement in the synthesis of thiophene derivatives. Some established methods have been modified and improved, while other novel methods have been discovered. Diverse catalysts were employed for these transformations. In some syntheses, reaction mechanisms were also displayed. Many methods for the synthesis of thiophenes have been developed recently. In the near future, more imaginative approaches for the synthesis of thiophenes will be investigated to improve the efficiency and versatility or the use of environmentally friendly and economical procedures for thiophene synthesis will be proposed. Application to natural product synthesis and drug synthesis is probably the next challenge in the field.