Mini-Reviews in Organic Chemistry - Volume 16, Issue 6, 2019

In this mini-review, the main synthetic routes used in the preparation of oxazolines is presented. The review is systematically carried out and the syntheses are presented in terms of precursors utilised (nitriles, aldehydes and carboxylic acids). Additionally, the reported synthesis of all chiral and achiral oxazolines involve either the use of amino alcohols as essential building blocks or some form of intramolecular cyclisation reactions. A comparison of the effectiveness of various reaction initiators such as Lewis acids, bases, oxidants and metals as well as their respective reaction conditions is also described. Lewis acid catalysts such as zinc chloride, zinc oxide and indium (III) chloride as well as triflic acid and ruthenium complexes are presented as effective catalysts in the formation of oxazolines from nitrile precursors. Oxidising agents such as N-bromosuccinimide, hypervalent iodine reagents and reducing agents such as butyllithium have been used in the formation oxazolines from aldehydes. While carboxylic acids have been used effectively as good precursors to oxazolines when using reagents such as cyanuric chloride as well as transition metal containing catalysts such as copper, ruthenium and titanium. In some cases, catalyst free reaction conditions have also been reported offering substituted oxazolines through microwave and ultrasonic irradiation as well as under standard reflux conditions.

During the last twenty years, our research group has been working with aromatic nitrosubstituted compounds acting as electrophiles in Polar Diels-Alder (P-DA) reactions with different dienes of diverse nucleophilicity. In this type of reaction, after the cycloaddition reaction, the nitrated compounds obtained as the [4+2] cycloadducts suffer cis-extrusion with the loss of nitrous acid and a subsequent aromatization. In this form, the reaction results are irreversible. On the other hand, the microwave-assisted controlled heating become a powerful tool in organic synthesis as it makes the reaction mixture undergo heating by a combination of thermal effects, dipolar polarization and ionic conduction. As the Diels-Alder (D-A) reaction is one of the most important process in organic synthesis, the microwave (MW) irradiation was applied instead of conventional heating, and this resulted in better yields and shorter reaction times. Several substituted heterocyclic compounds were used as electrophiles and different dienes as nucleophiles. Two experimental situations are involved: one in the presence of Protic Ionic Liquids (PILs) as solvent and the other under solvent-free conditions. The analysis is based on experimental data and theoretical calculations.

The β-lactams constitute a well-known class of compounds having tremendous biological significance. Besides being a motif of biological interest, they serve as versatile synthons in organic chemistry. In fact, their easy accessibility in the laboratory by several methods combined with inherent reactivity of the β -lactam ring due to ring-strain places it among the most sought for substrate in the arsenal of synthetic organic chemists. Several chemical reagents, heat, and light promote its ring-opening, ring-expansions and rearrangement reactions yielding a wide variety of biologically relevant nitrogen-containing acyclic and heterocyclic compounds. In recent years, the reactivity of differently functionalized β-lactam rings towards diverse kinds of reagents has been investigated. These investigations exploit selective bond cleavage of the β-lactam nucleus via N1-C2, C3- C4, C2-C3 or N1-C4 bond cleavage using simple reagents. The reduction of amide carbonyl group, thionation, and pyrolysis/photolysis have also been explored. These investigations have led to the discovery of many easy synthetic methods for biologically important classes of compounds such as β-amino acids, β-amino esters, amino sugars, amino alcohols, peptides, azetidines, and other heterocyclic compounds. This article discusses the advances made in the studies on the reactivity of β- lactam ring during the last ten years.

Coumarins are natural 1,2-benzopyrones, present in remarkable amounts as secondary metabolites in edible and medicinal plants. The low yield in the coumarins isolation from natural sources, along with the difficulties faced by the total synthesis, make them attractive for biotechnological studies. The current literature contains several reports on the biotransformation of coumarins by fungi, which can generate chemical analogs with high selectivity, using mild and eco-friendly conditions. Prompted by the enormous pharmacological interest in the coumarin-related compounds, their alimentary and chemical applications, this review covers the biotransformation of coumarins by filamentous fungi. The chemical structures of the analogs were presented and compared with those from the pattern structures. The main chemical reactions catalyzed the insertion of functional groups, and the impact on the biological activities caused by the chemical transformations were discussed. Several chemical reactions can be catalyzed by filamentous fungi in the coumarin scores, mainly lactone ring opening, C3-C4 reduction and hydroxylation. Chunninghamella sp. and Aspergillus sp. are the most common fungi used in these transformations. Concerning the substrates, the biotransformation of pyranocoumarins is a rarer process. Sometimes, the bioactivities were improved by the chemical modifications and coincidences with the mammalian metabolism were pointed out.

Crinnolines can serve as unique and versatile class of heterocycles especially in fields related to synthetic and pharmaceutical chemistry owing to their potent biological activities. They possess diversity of pharmaceutical activities as anticancer, antibacterial, anti-inflammatory, anti-allergic as well as anti-hypertensive activities. Since the first synthesis of cinnoline by Richter (1883) numerous protocols for their synthesis have been developed utilizing arenediazonium salts, aryl hydrazines and arylhydhydrazones precursors. Recently metal catalyzed C-C and C-N bond formation reactions have emerged as efficient tools for synthesis of cinnoline derivatives. This review aims to focus on the recent synthetic routes used for the synthesis of cinnoline derivatives. An effort has been carried out to provide an overview of practical methods for preparing cinnolines. Furthermore the reaction mechanisms have been described in brief.

In the recent years, an increasing attention has been given to the biological activities exerted by organoselenium compounds. In 1984, Sies reported for the first time the ability of ebselen to mimic the activity of glutathione peroxidase. From this milestone, several studies reported the pharmacological properties of selenium-containing compounds including their exploitation as antimicrobials. In this context, this minireview presents the most recent examples of seleno derivatives endowed with antimicrobial activities while discussing the most interesting and recent synthetic procedures used to obtain these compounds.

The quinoline nucleus is a very important class of heterocyclic aromatic compounds present in several drugs on the market, with synthetic methodologies being necessary to prepare its nucleus and derivatives. Considering that fact, the aim of this review is to describe the development of eco-friendly methodologies for the synthesis of quinoline nucleus and its derivatives in the last five years. Thus, throughout the text are presented varios reagents and catalysts used in the synthesis of quinoline nucleus, the reaction conditions, the advantages of the described methodologies, along with the reaction scheme and some reaction mechanisms.