Total Synthesis of Novel Skeleton Flavan-Alkaloids

Jing, Zhen; Simon, James E.; Wu, Qingli

doi:10.3390/molecules25194491

Cited by 4 publications

(9 citation statements)

References 17 publications

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“…The o -hydroxyacetophenone derivatives 11a – d were converted into the corresponding chalcones 13a – j by the Claisen–Schmidt condensation with the appropriate commercially available benzaldehydes 12a – d . , Flavanones 14a – j were synthesized by the intramolecular cyclization of 13a – j using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a base, followed by deprotection of the methoxymethyl (MOM) group in 14a – j to obtain the desired naringenin derivatives 1 – 10 as racemic compounds, as shown in Scheme . When methoxy groups were used as protecting groups, yields were extremely poor in the final step of demethylation.…”

Section: Results and Discussionmentioning

confidence: 99%

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis

et al. 2022

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Misfolding and aggregation of transthyretin are implicated in the fatal systemic disease known as transthyretin amyloidosis. Here, we report the development of a naringenin derivative bearing two chlorine atoms that will be efficacious for preventing aggregation of transthyretin in the eye. The amyloid inhibitory activity of the naringenin derivative was as strong as that of tafamidis, which is the first therapeutic agent targeting transthyretin in the plasma. X-ray crystal structures of the compounds in complex with transthyretin demonstrated that the naringenin derivative with one chlorine bound to the thyroxine-binding site of transthyretin in the forward mode and that the derivative with two chlorines bound to it in the reverse mode. An ex vivo competitive binding assay showed that naringenin derivatives exhibited more potent binding than tafamidis in the plasma. Furthermore, an in vivo pharmacokinetic study demonstrated that the dichlorinated derivative was significantly delivered to the eye.

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Section: Results and Discussionmentioning

confidence: 99%

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis

et al. 2022

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“…The molecular formulae of the parent ion and the various daughter ions (fragments) are given in Table 1. In order to confirm the attribution of these compounds as kinkeloids, fraction 2 was also analyzed by 1D and 2D NMR and compared with the chemical shifts of kinkeloids A-D [26,27]. Kinkeloids A, B, C, and D, flavonoid alkaloids discovered from CM, consisting of a flavan moiety with a piperidine ring attached at either the 6 or 8 position, have been described and differ only in the number of hydroxyl groups attached, resulting in consecutive mass unit differences in the mass spectra.…”

Section: Fractionation Msms and Nmr Analysesmentioning

confidence: 99%

Metabolite Profiling and Molecular Network Shows Kinkeloids as Promoting of Collagen Synthesis from Combretum micranthum

Messaili,

Haggouch,

Bignard

et al. 2024

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Combretum micranthum, a plant native to Africa, has a well-documented traditional use in the treatment of various ailments such as fever, diabetes, and malaria. Its pharmaceutical benefits include nephroprotective, anti-inflammatory, antioxidant, and antimicrobial properties, which were proven. In addition, its potential for cosmetic applications is being explored due to its depigmenting, anti-inflammatory, and UV-damage-repairing properties. This article investigates the molecular composition and new cosmetically relevant biological activity of C. micranthum and enriched fractions to begin the establishment of the structure–activity relationship. Firstly, an extract of C. micranthum was prepared and selected for its overall biological response and then fractionated to obtain simplified molecular fractions. One fraction was particularly enriched in kinkeloids, a specific family of compounds to this species. All the fractions and the crude extract were then tested on biological targets to evaluate and compare their cosmetic activities. Molecular networks were constructed from the UHPLC-MS/HRMS data to better characterize the extract and fractions and to highlight structure–activity relationships. This study highlights the metabolic profiling of a butylene glycol extract of C. micranthum, showing its main chemical families and revealing that the kinkeloids, identified by HRMS and NMR, promote an increase in collagen I synthesis, an interesting cosmetic activity neither previously described for these compounds and neither for C. micranthum extract.

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“…Piperidine-flavan alkaloids are not known from other plants. The combination of a flavan unit with a piperidine alkaloid can make flavan-piperidine alkaloids particularly biologically active [194]. According to a qualitatitive screening of the alkaloids in a leaf extract of C. dolichpetalum, the extract contained quinolone, isoquinoline, tropane, purine, and indole alkaloids [195].…”

Section: Alkaloidsmentioning

confidence: 99%

“…The pyrrolidine alkaloid, combretine, and the piperidine alkaloid betonicine have been isolated from the leaves of C. micranthum. In two different studies, a large number of piperidine-flavan alkaloids-the kinkeloids, with a completely new basic molecular structure consisting of a piperidine unit attached to the 6-or 8-carbon of the flavan backbone-were found in leaf extracts of C. micranthum (Figure 8) [27,45,194]. Kinkeloids of the A-, B-, C-, and D-series were characterized.…”

Section: Alkaloidsmentioning

confidence: 99%

Ethnopharmacology, Antimicrobial Potency, and Phytochemistry of African Combretum and Pteleopsis Species (Combretaceae): A Review

et al. 2023

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Bacterial and fungal resistance to antibiotics is of growing global concern. Plants such as the African Combretum and Pteleopsis species, which are used in traditional medicine for the treatment of infections, could be good sources for antimicrobial extracts, drug scaffolds, and/or antibiotic adjuvants. In African countries, plant species are often used in combinations as traditional remedies. It is suggested that the plant species enhance the effects of each other in these combination treatments. Thus, the multi-species-containing herbal medications could have a good antimicrobial potency. In addition, plant extracts and compounds are known to potentiate the effects of antibiotics. The objective of this review is to compile the information on the botany, ethnopharmacology, ethnobotany, and appearance in herbal markets of African species of the genera Combretum and Pteleopsis. With this ethnobotanical information as a background, this review summarizes the information on the phytochemistry and antimicrobial potency of the extracts and their active compounds, as well as their combination effects with conventional antibiotics. The databases used for the literature search were Scopus, Elsevier, EBSCOhost, PubMed, Google Scholar, and SciFinder. In summary, a number of Combretum and Pteleopsis species were reported to display significant in vitro antibacterial and antifungal efficacy. Tannins, terpenes, flavonoids, stilbenes, and alkaloids—some of them with good antimicrobial potential—are known from species of the genera Combretum and Pteleopsis. Among the most potent antimicrobial compounds are arjunglucoside I (MIC 1.9 µg/mL) and imberbic acid (MIC 1.56 µg/mL), found in both genera and in some Combretum species, respectively. The in vitro antimicrobial properties of the extracts and compounds of many Combretum and Pteleopsis species support their traditional medicinal uses.

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Total Synthesis of Novel Skeleton Flavan-Alkaloids

Cited by 4 publications

References 17 publications

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis

Metabolite Profiling and Molecular Network Shows Kinkeloids as Promoting of Collagen Synthesis from Combretum micranthum

Ethnopharmacology, Antimicrobial Potency, and Phytochemistry of African Combretum and Pteleopsis Species (Combretaceae): A Review

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