Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse ...responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.
According to the World Health Organization, the exacerbated use of antibiotics worldwide is increasing multi-resistant infections, especially in the last decade. Xanthones are a class of compounds ...receiving great interest in drug discovery and development that can be found as natural products or obtained by synthesis. Many derivatives of xanthones are chiral and associated with relevant biological activities, including antimicrobial. The aim of this review is to compile information about chiral derivatives of xanthones from natural sources and their synthesized examples with antimicrobial activity.
Stereoselective synthesis has been emerging as a resourceful tool because it enables the obtaining of compounds with biological interest and high enantiomeric purity. Flavonoids are natural products ...with several biological activities. Owing to their biological potential and aiming to achieve enantiomerically pure forms, several methodologies of stereoselective synthesis have been implemented. Those approaches encompass stereoselective chalcone epoxidation, Sharpless asymmetric dihydroxylation, Mitsunobu reaction, and the cycloaddition of 1,4-benzoquinone. Chiral auxiliaries, organo-, organometallic, and biocatalysis, as well as the chiral pool approach were also employed with the goal of obtaining chiral bioactive flavonoids with a high enantiomeric ratio. Additionally, the employment of the Diels-Alder reaction based on the stereodivergent reaction on a racemic mixture strategy or using catalyst complexes to synthesise pure enantiomers of flavonoids was reported. Furthermore, biomimetic pathways displayed another approach as illustrated by the asymmetric coupling of 2-hydroxychalcones driven by visible light. Recently, an asymmetric transfer hydrogen-dynamic kinetic resolution was also applied to synthesise (
)-
-alcohols which, in turn, would be used as building blocks for the stereoselective synthesis of flavonoids.
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•Membrane-assisted method is a promising alternative for large-scale chiral separation.•Polymeric membranes have some advantages over other methods.•Polymeric membranes with chiral ...porous materials can achieve high enantioselectivity.
The development and marked growth of chiral compounds is primarily due to the increased demand for pharmaceutical applications, but it has been also extended to other sectors like agrochemicals, food, flavours, fragrances and material science. The pure enantiomers can present higher efficacy, potency and are considered safer than racemate or even achiral compounds. Enantiomerically pure compounds can be obtained by stereoselective synthesis and by post-synthesis separation through chiral separation methodologies. The use of solid polymeric membranes has become promising for enantiomeric separation, due to the low cost and energy consumption, continuous operability and variety of materials. This review aims to present the advances in research of chiral separation, using the enantioseparation technique based on solid polymeric membranes. Theoretical fundamentals and applications of solid polymeric enantioselective membranes in the last ten years is presented. The review also provides relevant information on the performance of this type of membranes for future applications and improvement in chiral separation field.
The planning and development of new chiral stationary phases (CSPs) for liquid chromatography (LC) are considered as continuous and evolutionary issues since the introduction of the first CSP in ...1938. The main objectives of the development strategies were to attempt the improvement of the chromatographic enantioresolution performance of the CSPs as well as enlarge their versatility and range of applications. Additionally, the transition to ultra-high-performance LC were underscored. The most recent strategies have comprised the introduction of new chiral selectors, the use of new materials as chromatographic supports or the reduction of its particle size, and the application of different synthetic approaches for preparation of CSPs. This review gathered the most recent developments associated to the different types of CSPs providing an overview of the relevant advances that are arising on LC.
Chirality is a geometric property associated with the asymmetry of tridimensional features that accompanies our daily life at macroscopic as well as microscopic molecular levels ....
Flavonoids are a group of natural products with a great structural diversity, widely distributed in plant kingdom. They play an important role in plant growth, development and defense against ...aggressors. Flavonoids show a huge variety of biological activities such as antioxidant, anti-inflammatory, anti-mutagenic, antimicrobial and antitumor, being able to modulate a large diversity of cellular enzymatic activities. Among natural flavonoids, some classes comprise chiral molecules including flavanones, flavan-3-ols, isoflavanones, and rotenoids, which have one or more stereogenic centers. Interestingly, in some cases, individual compounds of enantiomeric pairs have shown different antitumor activity. In nature, these compounds are mainly biosynthesized as pure enantiomers. Nevertheless, they are often isolated as racemates, being necessary to carry out their chiral separation to perform enantioselectivity studies. Synthetic chiral flavonoids with promising antitumor activity have also been obtained using diverse synthetic approaches. In fact, several new chiral bioactive flavonoids have been synthesized by enantioselective synthesis. Particularly, flavopiridol was the first cyclin-dependent kinase (CDK) inhibitor which entered clinical trials. The chiral pool approaches using amino acid as chiral building blocks have also been reported to achieve small libraries of chrysin derivatives with more potent in vitro growth inhibitory effect than chrysin, reinforcing the importance of the introduction of chiral moieties to improve antitumor activity. In this work, a literature review of natural and synthetic chiral flavonoids with antitumor activity is reported for the first time.
This work reviews the contributions of the corresponding author (M.M.M.P.) and her research group to Medicinal Chemistry concerning the isolation from plant and marine sources of xanthone derivatives ...as well as their synthesis, biological/pharmacological activities, formulation and analytical applications. Although her group activity has been spread over several chemical families with relevance in Medicinal Chemistry, the main focus of the investigation and research has been in the xanthone family. Xanthone derivatives have a variety of activities with great potential for therapeutic applications due to their versatile framework. The group has contributed with several libraries of xanthones derivatives, with a variety of activities such as antitumor, anticoagulant, antiplatelet, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective, antioxidant, and multidrug resistance reversal effects. Besides therapeutic applications, our group has also developed xanthone derivatives with analytical applications as chiral selectors for liquid chromatography and for maritime application as antifouling agents for marine paints. Chemically, it has been challenging to afford green chemistry methods and achieve enantiomeric purity of chiral derivatives. In this review, the structures of the most significant compounds will be presented.
Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of ...legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can also be found in environmental samples and revealed to be useful for determination of community drug usage (sewage epidemiology), identification of illicit drug manufacturing locations, illegal discharge of sewage and in environmental risk assessment. Thus, the purpose of this paper is to provide an overview of the application of chiral analysis in biological and environmental samples and their relevance in the forensic field. Most frequently analytical methods used to quantify the enantiomers are liquid and gas chromatography using both indirect, with enantiomerically pure derivatizing reagents, and direct methods recurring to chiral stationary phases.
A systematic study of enantioresolution of a library of xanthonic derivatives, prepared "in-house", was successfully carried out with four commercially available macrocyclic glycopeptide-based ...columns, namely Chirobiotic
T, Chirobiotic
R, Chirobiotic
V and Chirobiotic
TAG. Evaluation was conducted in multimodal elution conditions: normal-phase, polar organic, polar ionic and reversed-phase. The effects of the mobile phase composition, the percentage of organic modifier, the pH of the mobile phase, the nature and concentration of different mobile phase additives on the chromatographic parameters are discussed. Chirobiotic
T and Chirobiotic
V, under normal-phase and reversed-phase modes, respectively, presented the best chromatographic parameters. Considering the importance of understanding the chiral recognition mechanisms associated with the chromatographic enantioresolution, and the scarce data available for macrocyclic glycopeptide-based columns, computational studies by molecular docking were also carried out.
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