Selected applications of Meldrum's acid – a tutorial

Brosge, Felix; Singh, Pardeep; Almqvist, Fredrik; Bolm, Carsten

doi:10.1039/d1ob00395j

Cited by 31 publications

(15 citation statements)

References 64 publications

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“…As delineated in Figure 1 , 3-hydroxypalmitic acid 7 was the key intermediate for the production of commendamide 1a . Several methods for the synthesis of 3-hydroxy carboxylic acids are reported in the literature and they mainly use the Reformatsky reaction ( Gawrorisk, 1984 ) or the reduction of β -ketoesters obtained by acylation of Meldrum’s acid ( Oikawa et al, 1978 ; Hodgkinson et al, 2011 ; Brinkerhoff et al, 2014 ; Brosge et al, 2021 ) or γ -alkylation of acetoacetate ( Smith et al, 2009 ). Here, we started from the reaction between the commercially available Meldrum’s acid 3 and myristoyl chloride 4 .…”

Section: Resultsmentioning

confidence: 99%

Facile and Sustainable Synthesis of Commendamide and its Analogues

2022

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Commendamide, or N-(3-hydroxypalmitoyl)-glycine 1a, is a gut microbiota-derived bioactive metabolite, structurally similar to long-chain N-acyl-amino acids which belong to the complex lipid signaling system known as endocannabinoidome and play important roles in mammals through activation of, inter alia, G-protein-coupled receptors (GPCRs). In this work, we describe a simple, green and economic method for the preparation of commendamide 1a, a GPCR G2A/132 agonist. The developed protocol is general and could also be applied to the synthesis of deuterated commendamide 1b, as well as to other minor microbiota-derived metabolites, such as the analog 2.

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Section: Resultsmentioning

confidence: 99%

Facile and Sustainable Synthesis of Commendamide and its Analogues

2022

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“…Although it was discovered more than a century ago, its use continues to attract the attention of synthetic chemists. Electrophilicity, dienophilicity, and its relatively low acidity (pKa = 4.9) make Meldrum’s acid attractive and quite useful for a wide number of synthetic manipulations such as heterocycles synthesis, Friedel-Crafts acylation, total synthesis, alkylidene and asymmetric synthesis, domino reactions, and catalytic additions [ 4 , 5 ]. Furthermore, Meldrum’s acid represents an essential molecule in the synthesis of natural products and analogues [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Biological Evaluation of Meldrum’s Acid Derivatives: Dual Activity and Molecular Docking Study

et al. 2023

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In the presented study, eight novel Meldrum’s acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum’s acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 μM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 μM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

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“…In order to obtain more excellent active lead molecules, four series of guaiazulene derivatives ( Figure 1) were designed and synthesized according to pharmacophore combination theory. Series I ( Scheme 1) was designed by combination of guaiazulene and cytotoxic bioactive methylene components such as Meldrum's acid, [16] cyanoacetic acid, [17] barbiturate, [18] rhodamine, [19] and so on. Designation of series II ( Scheme 2) was originated from guaiazulene based sulfonamide derivatives with remarkable anti‐inflammatory antitumor activities.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Activity of Guaiazulene Derivatives

Han

Ren

et al. 2023

Chemistry & Biodiversity

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Guaiazulene and related derivatives were famous for diverse biological activities. In an effort to discover new highly efficient candidate drugs derived from guaiazulene, four series of guaiazulene derivatives were designed, synthesized, and evaluated for antiproliferation, antiviral, anti-inflammatory and peroxisome proliferatorsactivated receptor γ (PPARγ) signalling pathway agonist activities. Among them, two guaiazulene condensation derivatives showed selective cytotoxic activities towards K562 cell with IC 50 values 5.21 μM and 5.14 μM, respectively, accompanied by slight effects on normal cell viability. For the first time, one guaiazulene derivative from series I exhibited potent antiviral activity towards influenza A virus with IC 50 of 17.5 μM. A guaiazulenebased chalcone showed higher anti-inflammatory activity than positive drug indomethacin with an inhibitory rate of 34.29 % in zebrafish model in vivo. One guaiazulene-based flavonoid could strongly agitate PPARγ pathway at 20 μM, indicating the potential of guaiazulene derivatives to reduce obesity development and ameliorate hepatic steatosis. Preliminary in silico ADME studies predicted the excellent drug-likeness properties of bioactive guaiazulene derivatives.

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Selected applications of Meldrum's acid – a tutorial

Abstract: Due to its unique structure and the vast array of substituents that can be attached to its core, Meldrum’s acid is a molecule with exceptional chemical properties. In water, it...

Cited by 31 publications

References 64 publications

Facile and Sustainable Synthesis of Commendamide and its Analogues

Facile and Sustainable Synthesis of Commendamide and its Analogues

Synthesis, Characterization, and Biological Evaluation of Meldrum’s Acid Derivatives: Dual Activity and Molecular Docking Study

Design, Synthesis, and Biological Activity of Guaiazulene Derivatives

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