- A large scale synthesis of a natural antibiotic, 2,4- diacetylophloroglucinol (DAPG)
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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 chromatographi
- Zakrzewski, Jerzy,Karpinska, Monika,Malinski, Zbigniew
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- Synthesis and P-glycoprotein induction activity of colupulone analogs
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Brain amyloid-beta (Aβ) plaques are one of the primary hallmarks associated with Alzheimer's disease (AD) pathology. Efflux pump proteins located at the blood-brain barrier (BBB) have been reported to play an important role in the clearance of brain Aβ, among which the P-glycoprotein (P-gp) efflux transporter pump has been shown to play a crucial role. Thus, P-gp has been considered as a potential therapeutic target for treatment of AD. Colupulone, a prenylated phloroglucinol isolated from Humulus lupulus, is known to activate pregnane-X-receptor (PXR), which is a nuclear receptor controlling P-gp expression. In the present work, we aimed to synthesize and identify analogs of colupulone that are potent P-gp inducer(s) with an ability to enhance Aβ transport across the BBB. A series of colupulone analogs were synthesized by modifications at both prenyl as well as acyl domains. All compounds were screened for P-gp induction activity using a rhodamine 123 based efflux assay in the P-gp overexpressing human adenocarcinoma LS-180 cells, wherein all compounds showed significant P-gp induction activity at 5 μM. In the western blot studies in LS-180 cells, compounds 3k and 5f were able to induce P-gp as well as LRP1 at 1 μM. The effect of compounds on the Aβ uptake and transport was then evaluated. Among all tested compounds, diprenylated acyl phloroglucinol 5f displayed a significant increase (29%) in Aβ transport across bEnd3 cells grown on inserts as a BBB model. The results presented here suggest the potential of this scaffold to enhance clearance of brain Aβ across the BBB and thus its promise for development as a potential anti-Alzheimer agent.
- Bharate, Jaideep B.,Batarseh, Yazan S.,Wani, Abubakar,Sharma, Sadhana,Vishwakarma, Ram A.,Kaddoumi, Amal,Kumar, Ajay,Bharate, Sandip B.
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- Diacylphloroglucinol derivatives as antioxidant agents: green synthesis, optimisation, in?vitro, and in silico evaluation
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Several derivatives of diacylphloroglucinol (3a–3c and 5a–5b) as an analogue of natural product compound 2,4-diacetylphloroglucinol 3a, were successfully synthesised in an excellent yield via a greener Friedel–Craft acylation using methanesulfonic acid (MSA) as a catalyst under an ultrasound-assisted condition. Operational simplicity, excellent yield, expedient metal-free synthesis, energy-efficient and mild reaction conditions are the outstanding advantages in this procedure. A scaled-up reaction also revealed the practical suitability of this newly developed procedure. The effects of several process variables on 3a were carefully accomplished using response surface methodology (RSM). Moreover, the green credentials of the present protocol have been assessed using several established green metrics and compared to relevant procedures. Along with the monomers, dimeric diacylphloroglucinols (6a–6e) were also synthesised and their in?vitro antioxidant activity of these species were carried out. Furthermore, drug-likeness, density functional theory (DFT), and molecular docking studies were also established.
- Prasetyo, Wahyu E.,Kusumaningsih, Triana,Firdaus, Maulidan,Marliana, Soerya D.,Suryanti, Venty,Artanti, Anif N.,Apriana, Ita,Anggraini, Septin D.
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- Convenient synthesis of 2,4-diacetylphloroglucinol a natural antibiotic involved in the control of take-all disease of wheat
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2,4-Diacetylphloroglucinol (DAPG) is an antibiotic with broad-spectrum antibacterial and antifungal activities. It is a major determinant in the biological control of several plant diseases. DAPG is produced by Pseudomonas fluorescens both in vitro and in the rhizosphere of wheat. It is involved in the natural suppression of take-all disease known as take-all decline, which develops in soils following extended monoculture of wheat or barley. A one- step synthesis of DAPG from the commercially available 2- acetytlphloroglucinol is described. This reaction involves the direct alkylation of 2-acetylphloroglucinol using acetic anhydride as the acetylation reagent, with boron trifluoride-etherate as the catalyst. This synthesis is simple and produces higher yields of DAPG (90%) as compared with previously described procedures. As ecological concerns are gaining equal status with agricultural concerns, the demand for natural biocontrol measures is increasing. There is tremendous pressure from society on agriculture to reduce the use of pesticides. A discussion is given on the agricultural and ecological importance of this natural antibiotic and its application as an alternative to reduce the use of synthetic pesticides.
- Marchand, Patrice A.,Weller, David M.,Bonsall, Robert F.
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- Highly efficient and green synthesis of diacylphloroglucinol over treated natural zeolite mordenite and the optimization using response surface method (RSM)
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Herein, we report a greener and highly efficient route for the Friedel-Craft acylation of phloroglucinol over Indonesian treated natural zeolite mordenite (nHZMOR) catalyst to provide value-added diacylphloroglucinol derivatives under solvent-free conditi
- Prasetyo, Wahyu Eko,Kusumaningsih, Triana,Firdaus, Maulidan
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- 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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Efforts toward the development of a straightforward greener Gram-scale synthesis of the antibiotic compound 2,4-diacetylphloroglucinol (DAPG) have been developed. This beneficial procedure was accomplished through the Friedel-Crafts acylation of phloroglucinol over inexpensive heterogeneous silica sulphuric acid (SSA) catalystviaultrasound-assisted (US) synthesis under solvent-free condition. The influences of various parameters such as temperature, catalyst loading, and reaction time on the reaction performance were analysed using a multivariate statistical modelling response surface methodology (RSM). A high yield ofDAPG(95%) was achieved at 60 °C after 15-20 min reaction with the presence of 10% (w/w)SSAas the catalyst. Column chromatography-free and a Gram scale-up reaction also exhibited the practical applicability of this newly developed protocol. TheSSAcatalyst was recovered and recycled up to 10 consecutive runs with no appreciable loss of activity. A plausible mechanism for the Friedel-Crafts acylation of phloroglucinol is proposed. Moreover, an environmental assessment has been carried out over this present method and compared with several established literature using the EATOS software and the Andraos algorithm to assess the consumption of the substrates, solvents, catalysts, and the production of coupled products or by-products. In addition, their energy consumptions were also determined. The data collected showed that the present method is the most promising one, characterised by the highest environmental impact profile against all the other reported methods. The physicochemical properties of the synthesisedDAPGwere assessed and exhibited reasonable oral bioavailability drug property as determined by Lipinski's rules.
- Firdaus, Maulidan,Kusumaningsih, Triana,Prasetyo, Wahyu Eko
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- Toward an efficient and eco-friendly route for the synthesis of dimeric 2,4-diacetyl phloroglucinol and its potential as a SARS-CoV-2 main protease antagonist: Insight from: In silico studies
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As a consequence of the unavailability of an anti-viral drug for SARS-CoV-2, the prospect of developing an antiviral drug is of great importance in this current emergency of the COVID-19 pandemic era. To support the enduring research on the improvement of
- Kusumaningsih, Triana,Prasetyo, Wahyu E.,Wibowo, Fajar R.,Firdaus, Maulidan
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supporting information
p. 7830 - 7843
(2021/05/13)
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- Total synthesis of dryocrassin ABBA and its analogues with potential inhibitory activity against drug-resistant neuraminidases
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The stems of Dryopteris crassirhizoma, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin ABBA is a key antiviral component in the herbal medicine while the compound is hard to
- Hou, Bo,Liu, Ze,Yang, Xiao-Bei,Zhu, Wen-Fei,Li, Jin-Yu,Yang, Liu,Reng, Fu-Cai,Lv, Yong-Feng,Hu, Jiang-Miao,Liao, Guo-Yang,Zhou, Jun
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p. 3846 - 3852
(2019/07/18)
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- 2. 4 - Diacetyl phloroglucinol analogue and its preparation method and application
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The invention discloses a 2,4-DAPG analogue and a preparation method and application thereof. The structure of the 2,4-DAPG analogue is shown as the formula (1) or formula (2), wherein R is C2-C15 alkyl, R1 and R2 are C1-C15 alkyl, and the R1 and the R2 a
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Paragraph 0024; 0031; 0050
(2018/05/30)
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- 2,4-diacetyl phloroglucinol ester compound and bactericidal application thereof
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The invention relates to a 2,4-diacetyl phloroglucinol ester compound and a bactericidal application thereof. The structural formula of the compound is shown as formula I. The 2,4-diacetyl phloroglucinol ester compound provided by the invention has strong
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Paragraph 0024; 0025; 0026; 0027; 0028
(2017/07/21)
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- Biocatalytic Friedel–Crafts Acylation and Fries Reaction
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The Friedel–Crafts acylation is commonly used for the synthesis of aryl ketones, and a biocatalytic version, which may benefit from the chemo- and regioselectivity of enzymes, has not yet been introduced. Described here is a bacterial acyltransferase which can catalyze Friedel–Crafts C-acylation of phenolic substrates in buffer without the need of CoA-activated reagents. Conversions reach up to >99 %, and various C- or O-acyl donors, such as DAPG or isopropenyl acetate, are accepted by this enzyme. Furthermore the enzyme enables a Fries rearrangement-like reaction of resorcinol derivatives. These findings open an avenue for the development of alternative and selective C?C bond formation methods.
- Schmidt, Nina G.,Pavkov-Keller, Tea,Richter, Nina,Wiltschi, Birgit,Gruber, Karl,Kroutil, Wolfgang
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supporting information
p. 7615 - 7619
(2017/06/13)
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- Spectrometric assay for horseradish peroxidase activity based on the linkage of conjugated system formed by oxidative decarboxylation
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Horseradish peroxidase (HRP)-catalyzed oxidation of 2,2-bis[3-acethylfilicinic acid-5-yl]acetic acid (BAFA, 4) produces Dehydro-3,3’-diacetyl-5,5’-methylenedifilicinic acid (DDMF, 3). A new photometric hydrogen donor (4) for peroxidase (POD)-catalyzed oxi
- Yamaguchi, Masaki,Sato, Shingo
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p. 189 - 194
(2016/12/27)
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- One pot synthesis and anticancer activity of dimeric phloroglucinols
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A series of dimeric phloroglucinol compounds were synthesized in a single step using commercially available phloroglucinol and methanesulfonic acid. Based on the reported anticancer activity of plant derived dimeric phloroglucinols, these synthesized comp
- Chauthe, Siddheshwar K.,Bharate, Sandip B.,Periyasamy, Giridharan,Khanna, Amit,Bhutani, Kamlesh K.,Mishra, Prabhu D.,Singh, Inder P.
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experimental part
p. 2251 - 2256
(2012/05/04)
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- Tandem one-pot synthesis of flavans by recyclable silica-HClO4 catalyzed Knoevenagel condensation and [4 + 2]-Diels-Alder cycloaddition
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An efficient one-pot multi-component synthesis of flavans using perchloric acid supported on silica as a recyclable heterogeneous catalyst has been described. This is the first report of direct one-step construction of a flavan skeleton from a phenolic precursor. The method involves a Knoevenagel-type condensation leading to in situ formation of transient O-quinone methide which further undergoes [4 + 2]-Diels-Alder cycloaddition with styrene to yield a flavan skeleton. The method provides easy access to a wide range of bio-active natural products viz. flavonoids, anthocyanins and catechins.
- Bharate, Sandip B.,Mudududdla, Ramesh,Bharate, Jaideep B.,Battini, Narsaiah,Battula, Satyanarayana,Yadav, Rammohan R.,Singh, Baldev,Vishwakarma, Ram A.
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experimental part
p. 5143 - 5150
(2012/08/08)
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- Ortho-amidoalkylation of phenols via tandem one-pot approach involving oxazine intermediate
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A new and efficient method for ortho-amidoalkylation of phenols via Mannich-type condensation with formaldehyde and lactams using recyclable solid acid catalyst is described. This is the first report for ortho-amidoalkylation of phenols by lactams via Mannich-type condensation. LC-ESI-MS/MS based mechanistic study revealed that reaction proceeds through o-quinone methide (o-QM) and an oxazine intermediate via tandem Knoevenagel condensation, formal [4 + 2]-Diels-Alder cycloaddition and acid catalyzed oxazine ring-opening.
- Mudududdla, Ramesh,Jain, Shreyans K.,Bharate, Jaideep B.,Gupta, Ajai P.,Singh, Baldev,Vishwakarma, Ram A.,Bharate, Sandip B.
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p. 8821 - 8827
(2012/11/07)
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- Molecular and catalytic properties of monoacetylphloroglucinol acetyltransferase from pseudomonas sp. YGJ3
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Monoacetylphloroglucinol (MAPG) acetyltransferase, catalyzing the conversion of MAPG to 2,4-diacetylphloroglucinol (DAPG), was purified from Pseudomonas sp. YGJ3 grown without Cl-. Cl- and pyoluteorin repressed expression of the enzyme. SDS-polyacrylamide gel electrophoresis showed that the purified enzyme (Mr = 330 kDa) was composed of three subunits of 17, 38, and 43 kDa, and protein sequencing identified these as PhlB, PhlA, and PhlC respectively. The enzyme catalyzed the reversible disproportionation of 2 moles of MAPG to phloroglucinol (PG) and DAPG. The equilibrium constant K (=[DAPG][PG]/[MAPG]2) was estimated to be about 1.0 at 25°C. A KpnI 20-kb DNA fragment was cloned from the genomic DNA of strain YGJ3, and a 12,598-bp long DNA region containing the phl gene cluster phlACBDEFGHI was sequenced. PCR cloning and expression of the phl genes in Escherichia coli confirmed that expression of phlACB genes produced MAPG ATase.
- Hayashi, Asuka,Saitou, Hiroki,Mori, Tomomi,Matano, Ikue,Sugisaki, Hiroyuki,Maruyama, Kiyofumi
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experimental part
p. 559 - 566
(2012/06/15)
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- Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect
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Besides 2′,4′-dihydroxy-4,6′-dimethoxy-3′-prenylchalcone (1) and 4-acetoxy-2′,4′-dihydroxy-6′-methoxy-3′-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3′-coumaroyl-2′,4,4′-trihydroxy-6′-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3′ was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3 ± 0.4 μM. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7 ± 0.3 and 6.0 ± 1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 μM the TNFα induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively.
- Vogel, Susanne,Barbic, Matej,Jürgenliemk, Guido,Heilmann, J?rg
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experimental part
p. 2206 - 2213
(2010/08/07)
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- Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols
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Plants are an important source of a variety of bioactive compounds with different modes of action. Anti-HIV agents from plant sources can be useful in developing novel therapies for inhibiting HIV infection. Based on the reported anti-HIV activity of plant derived phloroglucinols, several new dimeric phloroglucinols were synthesized in the present study by varying substitution on aromatic ring and at methylene bridge. Some of the synthesized compounds have shown good HIV inhibitory activity in a human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL4.3 virus isolate. Structure-activity studies indicate that phenyl, 4-benzyloxy-1-phenyl and cyclohexyl substitution at methylene bridge gave compounds with better anti-HIV activity. Compounds 22 and 24 showed highest anti-HIV activity with an IC50 of 0.28 μM and 2.71 μM, respectively, former was more active than the positive standard AZT in cell based assay.
- Chauthe, Siddheshwar K.,Bharate, Sandip B.,Sabde, Sudeep,Mitra, Debashis,Bhutani, Kamlesh K.,Singh, Inder P.
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body text
p. 2029 - 2036
(2010/06/12)
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- Desmosdumotins, the Method for Preparing the Same and Use as Anti-Tumor or Anti-AIDS Agents
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This invention discloses the method for preparing desmosdumotin C, the series of desmosdumotin C derivatives and their manufactures, and the total synthesis of desmosdumotin B. The invention also discloses uses of the derivatives and pharmaceutical compos
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Page/Page column 12
(2009/09/28)
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- Concise synthesis of chafurosides A and B
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The regioselective synthesis of chafurosides A (1) and B (2) from the same methyl ketone 5 was accomplished using a novel protecting group strategy. Both flavone rings were constructed from β-diketone intermediate 4, which was readily obtained by condensation of an acyl donor and ketone 5. Construction of the dihydrofuran ring was achieved via an intramolecular Mitsunobu reaction.
- Furuta, Takumi,Nakayama, Miho,Suzuki, Hirotaka,Tajimi, Hiroko,Inai, Makoto,Nukaya, Haruo,Wakimoto, Toshiyuki,Kan, Toshiyuki
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supporting information; experimental part
p. 2233 - 2236
(2009/10/02)
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- Antitumor agents 243. Syntheses and cytotoxicity of desmosdumotin C derivatives
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New analogs of desmosdumotin C (1), in which other aromatic rings replaced the terminal phenyl group and the A-ring was modified, were synthesized. Compounds 2-9, 13, and 16 were evaluated in vitro against human tumor cell replication. The 4-bromophenyl a
- Nakagawa-Goto, Kyoko,Wu, Jiu-Hong,Bastow, Kenneth F.,Wu, Chin-Chung,Lee, Kuo-Hsiung
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p. 2325 - 2330
(2007/10/03)
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- Efficient synthesis of analogs of safflower yellow B, carthamin, and its precursor: Two yellow and one red dimeric pigments in safflower petals
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The synthesis of analogs (8, 12, 14) of two yellow pigments, safflower yellow B and the precursor of carthamin, and carthamin itself, a red pigment, which are produced in safflower (Carthamus tinctrious L.) petals and, which have a common dimeric quinocha
- Sato, Shingo,Kusakari, Takashi,Suda, Tohru,Kasai, Takaharu,Kumazawa, Toshihiro,Onodera, Jun-Ichi,Obara, Heitaro
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p. 9630 - 9636
(2007/10/03)
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- Conversion of diacetyl-C-(β-D-glucopyranosyl)phloroglucinol to spiroketal compounds
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Diacetyl-C-(β-D-glucopyranosyl)phloroglucinol was converted by refluxing in water to spiro(benzofuran-[2H]furan) a new compound, along with spiro(benzofuran-[2H]pyran). The stereochemistry of the quaternary carbon of both spiro compounds had an S-configuration.
- Sato, Shingo,Kumazawa, Toshihiro,Watanabe, Ko-Ichi,Matsuba, Shigeru,Onodera, Jun-Ichi
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p. 429 - 433
(2007/10/03)
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- Inhibitory effect of acylphloroglucinol derivatives on the replication of vesicular stomatitis virus.
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The antiviral activity of natural phloroglucinols and of synthesized mono- and diacylphloroglucinols, and 2,6-diacyl-4,4-dialkylcyclohexa-1,3,5-triones was investigated. A correlation between the acyl chain length and inhibitory activity against vesicular stomatitis virus (VSV) was observed. Potent antiviral activity was found in di-isovalerylphoroglucinol. 2,6-Diacyl-4,4-dialkylcyclohexa-1,3,5-triones inhibited replication of the virus with low cytotoxicity.
- Chiba,Takakuwa,Tada,Yoshii
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p. 1769 - 1772
(2007/10/02)
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- Synthesis of Syzygiol; Skin-Tumor Promotion Inhibitor
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Syzygiol, 3-hydroxy-2-(β-hydroxycinnamoyl)-5-methoxy-6,6-dimethyl-2,4-cyclohexadien-1-one (1) was synthesized via ceroptene (5).
- Sato, Shingo,Obara, Heitaro,Endo, Akira,Onodera, Jun-ichi,Matsuba, Shigeru
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p. 2552 - 2554
(2007/10/02)
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- Analogues of natural phloroglucinols as antagonists against both thromboxane A2 and leukotriene D4
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Antagonists against both thromboxane A2 and leukotriene D4 were prepared from phloroglucinol. These compounds showed almost the same activity as the chinesins which were isolated from Hypericum chinense L. The correlation between the
- Tada,Chiba,Takakuwa,Kojima
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p. 1209 - 1212
(2007/10/02)
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- Reaction of Acetic Anhydride/Zinc Chloride Reagent with Phenols: Improved Yields of Hydroxyacetophenones
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Acetic anhydride/zinc chloride has been found to be a better acylating system for phenol and polyphenols resulting in improved yields of the respective hydroxyacetophenones.The phenols used are phenol, resorcinol, hydroquinonone, catechol, phloroglucinol and pyrogallol.With resorcinol the isomeric diacetyl derivatives are formed in excellent yields in a single step, while catechol and hydroquinone give only monoacetyl derivatives like simple phenol.Pyrogallol gives a monoacetyl derivative while phloroglucinol gives both mono and diacetyl derivatives but not triacetyl derivatives.
- Anjaneyulu, A. S. R.,Mallavadhani, U. V.,Venkateswarlu, Y.,Prasad, A. V. Rama
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p. 823 - 826
(2007/10/02)
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