A Large Scale Synthesis of a Natural Antibiotic, 2,4‐Diacetylophloroglucinol (DAPG)

Zakrzewski, Jerzy; Karpińska, Monika; Maliński, Zbigniew

doi:10.1002/ardp.200600139

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…In a smaller-scale reaction, we could identify mono-and trimethylated compounds 18 (7%) and 19 (2%) as minor side products. 20 When employing K 2 CO 3 , we observed faster trimethylation (19) than with Na 2 CO 3 , which required more careful reaction monitoring. 21 Condensation of 8 with 2,4-dimethoxybenzaldehyde (9) was conveniently possible at 45 °C in the presence of Ba(OH) 2 octahydrate in 2-butanone-free EtOH (Scheme 6).…”

Section: ■ Resultsmentioning

confidence: 91%

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Multigram, Chromatography-Free Synthesis of the Flavonol Morin

Gurzadyan

Mende

Schmid

et al. 2023

Org. Process Res. Dev.

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An inexpensive, five-step synthesis of the flavonol morin on a 40 g scale is described, a natural product that is used in electroplating processes. Comprehensive analysis of the products obtained in the oxidative cyclization of the chalcone precursor with alkaline tert-butyl hydroperoxide (TBHP) was performed. For the first time, the auronol isomer of tetramethylmorin was characterized, which prefers the hydroxybenzofuran tautomer. It is shown that the auronol is formed, at least in part, from the corresponding aurone. We were able to devise a work-up sequence that avoids chromatography for all reaction steps, employing technical-grade solvents. Recrystallization of the crude TBHP oxidation product from n-butanol allowed the removal of all components besides tetramethylmorin and the isomeric auronol, which were separated as their sodium salts.

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Section: ■ Resultsmentioning

confidence: 91%

“…Acetyl phloroglucinol 2 was obtained in 76% yield. As a minor side product, we observed diacetylated compound 17 (5%), which was separated after quenching with water (cooling! ), followed by filtration.…”

Section: Resultsmentioning

confidence: 99%

Multigram, Chromatography-Free Synthesis of the Flavonol Morin

Gurzadyan

Mende

Schmid

et al. 2023

Org. Process Res. Dev.

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“…Biological production of DAPG is usually slow with very low yield, but DAPG can be chemically synthesized, a production route amenable for industrial scale-up (Zakrzewski et al 2007 ). Thus, DAPG appears as bespoke bioentity with proven activity against enveloped viruses, fungal and bacterial pathogens which can be economically produced in purified form, tailor made to function, industrial-scale ready to make available in short span to control the COVID-19 pandemic as well as cross infection.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory efficacy of 2, 4-diacetylphloroglucinol against SARS-COV-2 proteins: in silico study

2022

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The pandemic of Severe Acute Respiratory Syndrome Coronavirus-2 has affected millions of people worldwide with common symptoms of fever, cough, and respiratory complications. The pandemic has posed a huge challenge to emergency health services due to unavailability of potent therapeutic drugs. The proteins associated with the viral pathogenesis has been identified as suitable targets for drug design and warrants effective drug discovery to abate COVID-19. The papain-like protease (PLpro), nucleocapsid (N), main protease (Mpro) and non-structural protein (nsp12) of SARS-CoV-2, key component of processing of viral polyproteins, transcription, assembly and replication. On this streak, present study evaluated the interaction of ligand 2,4-diacetylphloroglucinol (DAPG) with viral proteins using molecular docking with (i) AutoDock 4.2.6 and (ii) AutoDock Vina followed by molecular dynamic simulation studies of protein-ligand complex configuration. The analysis revealed that PLpro (3E9S) and N (4J3K) protein corresponds to the highest docking score and therefore, selected for molecular dynamics simulation study (100 ns). The study comprised analysis of parameters: (i) RMSD and RMSF, (ii) radius of gyration- which indicated interaction of protein entities with ligand supported steadiness of the complex, (iii) Coulombic and Lennard–Jones interactions, which played a significant role in complex stability. DAPG showed a good number of H-bonds with PLpro and MM-PBSA binding energy when compared to the N protein. This study showed DAPG as a potential bioactive molecule to act as an inhibitor for the PLpro thereby, DAPG can be used as potential inhibitor against SARS-CoV-2 and is potential drug candidate against COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s11756-021-00979-4.

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“…To date, a plethora of procedures have been reported for the synthesis of DAPG and acylated phloroglucinol that utilize AlCl 3 , 17,20 BF 3 -etherate, 5,20,22 and ZnCl 2 (ref. 22) as the catalyst.…”

Section: Introductionmentioning

confidence: 99%

A greatly improved procedure for the synthesis of an antibiotic-drug candidate 2,4-diacetylphloroglucinol over silica sulphuric acid catalyst: multivariate optimisation and environmental assessment protocol comparison by metrics

2020

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A Large Scale Synthesis of a Natural Antibiotic, 2,4‐Diacetylophloroglucinol (DAPG)

Abstract: A natural antibiotic, 2,4-diacetylophloroglucinol (DAPG), has been prepared by the acetylation of phloroglucinol (PhL) with acetic anhydride in the presence of boron trifluoride etherate complex. The crude DAPG is efficiently purified using chromatographic filtration with boiling eluent.

Cited by 7 publications

References 22 publications

Multigram, Chromatography-Free Synthesis of the Flavonol Morin

Multigram, Chromatography-Free Synthesis of the Flavonol Morin

Inhibitory efficacy of 2, 4-diacetylphloroglucinol against SARS-COV-2 proteins: in silico study

A greatly improved procedure for the synthesis of an antibiotic-drug candidate 2,4-diacetylphloroglucinol over silica sulphuric acid catalyst: multivariate optimisation and environmental assessment protocol comparison by metrics

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