Heterocyclic compounds form an important and extensive group of organic substances. Among nitrogenous heterocyclic molecules, quinolines stand out for exhibiting attractive chemical and biological properties. These substances can be used as ligands, sensors, luminescent and agrochemical materials. In addition, quinoline-containing compounds can exhibit a wide spectrum of pharmacological properties, allowing their use in several approved drugs nowadays. Due to its importance, the synthesis of molecules containing this nucleus becomes a point of interest for synthetic chemists. In this way, several methodologies have been recently developed to prepare quinoline derivatives with high structural diversity. Such chemical transformations allow the chemical modification of these rings with high selectivity and tolerance to diverse functional groups and these properties have been conveniently used in the preparation of biologically active molecules containing this unit. Herein, we present a review of the main methodologies employed in the selective functionalization of quinolines in the last twenty years. In this context, a brief introduction addressing general synthetic and medicinal aspects related to the functionalization positions of the quinoline ring is presented. Several methodologies used in the functionalization of this moiety are discussed, as well relevant synthetic applications, both in the preparation and functionalization of substances of biological interest.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led society to live with a serious public health problem. In this sense, repositioning of antiretrovirals has captured the attention of the scientific community. Tenofovir disoproxil fumarate (TDF) is an antiretroviral compound that is used to treat acquired immune deficiency syndrome (AIDS) and hepatitis B. In this short report, we present a scale-up investigation of TDF by in situ infrared spectroscopy monitoring and a forced degradation study to describe a new degradation product. Finally, we have evaluated TDF in vitro for SARS-CoV-2 for the first time foreseeing the using of this medicine in pre-clinical and clinical investigations for the COVID-19 (coronavirus disease 2019) treatment.

Currently, the pharmaceutical industry devotes great attention to drug degradation products because these compounds can offer risks to patients. A previous degradation study of betahistine (N-α-methyl-2-pyridylethylamine) conducted under different stress conditions detected three main impurities named A, B and C. Degradation products were analyzed by high-resolution mass spectrometry in electrospray source and time of flight analyzer (ESI-TOF) and nuclear magnetic resonance (NMR). Impurity mutagenicity was evaluated by Derek Nexus and Sarah Nexus softwares. Liquid chromatography hyphenate with tandem mass spectrometry (LC-MS/MS) analysis of the betahistine forced degradation sample indicated the presence of a new impurity, which was named impurity C1. 2D NMR experiments allowed the complete structural characterization of the new entity. The active pharmaceutical ingredient and degradation impurities were classified as inactive in the in silico mutagenic studies. Systematic investigation of a forced degradation sample led to the characterization of a new betahistine impurity. The in silico mutagenicity study of the betahistine degradation impurities may be useful in the risk assessment of the drug products.

The amorphous, mesoporous SiO2-SO3H catalyst with a surface area of 115 m2 g-1 and 1.32 mmol H+ per g was very efficient for the protonation of ketones on a 10% (m/m) basis, and the catalyst-bound intermediates can be trapped by polyalcohols to produce ketals in high yields or suffer aldol condensations within minutes under low-power microwave irradiation. The same catalyst can easily reverse the ketalization reaction.

Propacetamol is an acetaminophen prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy. After injection, it is completely converted by plasma esterases into N,N-diethylglycine and acetaminophen, its active metabolite whose mechanism of action is the inhibition of prostaglandin synthesis. Herein, we report an improved protocol for the synthesis of propacetamol hydrochloride that allows the isolation of the active pharmaceutical ingredient (API) with high purity and yield. In addition, the in vitro metabolism of propacetamol in a microssomal reaction was evaluated by ion trap tandem mass spectrometry.

Carbenoids are a class of highly reactive reagents that play an important role in modern organic synthesis. These species are very similar to singlet state carbenes since they have an ambiphilic character and react by a concerted mechanism allowing stereospecific transformations. Herein, we discuss these and other chemical aspects of zinc, lithium and magnesium carbenoids as well as relevant applications of these intermediates in organic synthesis.

As lignanas tetraidrofurânicas são metabólitos secundários com reconhecida atividade antiprotozoária. Na literatura, há vários relatos sobre os efeitos anti-parasitários de análogos sintéticos de lignanas contendo pontes de enxofre. Neste trabalho, foi realizada a síntese de análogos tiofênicos de lignanas com o uso de uma estratégia sintética seletiva e de alto desempenho baseada na reação de acoplamento cruzado de Negishi. Os derivados sintéticos foram obtidos de maneira rápida e apresentaram alto grau de pureza e baixa toxicidade para uma linhagem celular de mamífero e atividade leishmanicida com diferentes potências.

Lignans represent a well-known group of natural products with anti-protozoal activity. In the literature there are many examples of the anti-parasitic activity of synthetic analogues of lignans containing sulphur bridges. In this work, we have obtained thiophene-based analogues by using a selective and high performance synthetic strategy based on the Negishi cross-coupling reaction. The derivatives were quickly obtained and showed great purity, low toxicity toward a mammalian cell line, and leishmanicidal activity with different potencies.

Os enantiômeros (R) e (S) da Z-7,15-hexadecadien-4-olida (4), o feromônio sexual da Heptophylla picea foram sintetizados. Na etapa chave foi utilizada uma enantiolactonização já conhecida, intermediada por uma lipase, levando a um precursor comum de ambos enantiômeros do feromônio em 92% de e.e.

The (R) and the (S) enantiomers of the Z-7,15-hexadecadien-4-olide (4), the sex pheromone of Heptophylla picea, were synthesized. A known lipase-catalysed enantiolactonization in the key step afforded a common precursor for both enantiomers of the pheromone in 92% e.e.

A introdução de um grupamento equivalente ao ânion carboximetil a enonas e nitroalquenos através da reação de adição 1,4 do cianocuprato da 2,4,4-trimetil-2-oxazolina 3, resulta numa metodologia interessante para a síntese de produtos naturais como (±)-metil jasmonato (1) e (±)-baclofen (2).

Introduction of a synthon equivalent to a carboxymethyl anion to enones and nitroalkenes, through a 1,4-addition reaction of 2,4,4-trimethyl-2-oxazoline cyanocuprate 3, proved to be an interesting methodology for the synthesis of natural products such as (±)-methyl jasmonate (1) and (±)-baclofen (2).

This article summarizes how chiral 2-oxazolines have been employed as inducers of asymmetry in many kinds of organic reactions, including the more recent examples reported in which chiral bis(oxazolines) have been complexed in situ with transition metals and utilized to induce the stereoselectivity of some reactions.