Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

Pinto, Madalena; Fernandes, Carla; Tiritan, Maria Elizabeth

doi:10.3390/molecules25081931

Cited by 53 publications

(31 citation statements)

References 108 publications

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“…The enantiomeric purity was also evaluated being higher than 99%, except for trans- kielcorin C ( 61 ) [ 132 ]. It must be highlighted that the development of methods to obtain and analyse both pure enantiomers has been acquired crucial importance, as are required for biological and pharmacological activity evaluation of both enantiomers [ 133 ]. The inhibitory activity of the racemates C-E as well as of the corresponding enantiomers on in vitro growth of the human breast adenocarcinoma cell line MCF-7 was evaluated and compared.…”

Section: A Library Of Natural Mimetic Xanthones Looking For Biologmentioning

confidence: 99%

From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

et al. 2021

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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.

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Section: A Library Of Natural Mimetic Xanthones Looking For Biologmentioning

confidence: 99%

From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

et al. 2021

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“…Despite the remarkable achievements of the pharmaceutical field to produce chiral drugs, [79–80] there is a constant development to access enantioselective green approaches. This sustainable demand is also spread out for analytical techniques to discriminate enantiomers because of their costs, time‐consuming, and waste production.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of α‐Hydroxyphosphonates Containing Functionalized 1,2,3‐Triazoles

et al. 2020

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Herein, we described a simple and efficient protocol for the synthesis of α‐hydroxyphosphonates containing 1,2,3‐triazole moiety in their structures under mild conditions. This approach was performed by Abramov reaction in a solvent‐free system, using Na2CO3 as catalyst at 70 °C, which provided the desired products from moderate to excellent yields. The substrate scope was effective for different organic functions, such as ester, ketone, and amide. The synthetic route is modulated by the presence of a bulky group at the hydrophosphoryl reagent, avoiding steric hindrance, since the Abramov reaction can be approached before the Click‐Chemistry protocol. The synthesis can also be carried out in a one‐pot method, minimizing costs, and without side reactions. Additionally, the chiral discrimination of the synthesized products was easily accessed by 1H and 31P nuclear magnetic resonance experiments, using a chiral solvating agent.

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“…Separation of enantiomers has become a pivotal task in several research fields, including pharmaceutical and medicinal chemistry, 1 since enantiomers of drugs and promising bioactive compounds may have different pharmacokinetic and pharmacodynamic properties 2,3 as well as diverse toxicological effects 4,5 . These are the reasons why the regulatory authorities advocate more on strict investigation and requirements for evaluating the safety and efficacy of new drugs containing stereogenic centers 6 .…”

Section: Introductionmentioning

confidence: 99%

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies

Phyo¹,

Teixeira

Gonçalves

et al. 2021

Chirality

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Liquid chromatography enantioseparation and determination of enantiomeric purity of synthetized xanthone and benzophenone derivatives comprising one or more chiral moieties are reported. High enantioselectivity and resolution were observed in (S,S)‐Whelk‐O1 chiral stationary phase (CSP) for the enantiomeric mixtures of compounds comprising an aromatic ring linked to the stereogenic center(s), with α values ranging from 1.35 to 4.15 and Rs values ranging from 2.22 to 13.87. Among all the tested enantiomeric mixtures, those comprising three chiral moieties positioned in the xanthone scaffold gave the best chromatographic results. Enantiomers comprising an alkyl chain linked to the stereogenic centers were enantioseparated on a Lux® Celullose‐2 CSP. For both CSPs, the elution was performed in polar organic mode. The enantiomeric ratio (e.r.) values were always higher than 99%. Additionally, assessment of chiral recognition mechanisms on (S,S)‐Whelk‐O1 CSP was performed by molecular docking approach, which are in accordance with the chromatographic parameters. The nature and number of chiral moieties in the central aromatic scaffold of either xanthone or benzophenone derivatives are proved to be crucial for enantiorecognition. The evaluation of the growth inhibition of human tumor cell lines revealed that (S,S)‐(+)‐5 was the most potent compound, with values of GI50 of 12.83 ± 2.09 μM for A375‐C5 melanoma, 12.40 ± 1.16 μM for MCF‐7 breast adenocarcinoma, and 13.06 ± 1.29 μM for NCI‐H460 non‐small cell lung cancer. In some cases, the growth inhibitory effects demonstrated to be dependent on the stereochemistry of the compounds.

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Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

Cited by 53 publications

References 108 publications

From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

Synthesis of α‐Hydroxyphosphonates Containing Functionalized 1,2,3‐Triazoles

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies

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