129-24-8

Usage

Uses

Used in Pharmaceutical Industry:
Viridicatin is used as an anti-tuberculosis agent for its potent selective activity against Mycobacterium tuberculosis, making it a potential candidate for the development of new treatments for tuberculosis.
Used in Allergy Treatment:
Viridicatin, isolated from deep-sea Penicillium griseofulvum, is used as an anti-allergic agent for its ability to alleviate anaphylaxis and exhibit anti-allergic properties, offering a potential therapeutic option for individuals suffering from allergies.

InChI:InChI=1/C15H11NO2/c17-14-13(10-6-2-1-3-7-10)11-8-4-5-9-12(11)16-15(14)18/h1-9,17H,(H,16,18)

Upstream product

• 23207-75-2 N-(2-benzoylphenyl)-2-chloroacetamide 
• 2835-77-0 (2-aminophenyl)(phenyl)methanone 
• 26386-86-7 3-hydroxyquinolin-2(1H)-one 
• 91-56-5 indole-2,3-dione 
• 176170-14-2 4-bromo-3-hydroxyquinolin-2(1H)-one 
• 98-80-6 phenylboronic acid 
• 28565-95-9 3-hydroxy-3-phenylquinoline-2,4(1H,3H)-dione 
• 14933-29-0 4-hydroxy-3-phenyl-2(1H)-quinolone 
• 118-48-9 isatoic anhydride 
• 2566-30-5 N-Methyl-L-phenylalanine 
• 50886-63-0 (3S)-3,4-dihydro-4-methyl-3-phenylmethyl-[1,4]benzodiazepin-2,5(1H)-dione 
• 31965-37-4 3-benzylidene-4-methyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione 
• 19357-57-4 4-methyl-3'c-phenyl-(2'rN)-1H-spiro[benzo[e][1,4]diazepine-3,2'-oxirane]-2,5-dione 
• 3526-43-0 N-(4-methoxybenzyl)aniline 

Downstream Products

• 113843-74-6 bis(4-phenyl-3-hydroxy-2-quinolone)copper 
• 40357-47-9 3-methoxy-1-methyl-4-phenylquinolin-2(1H)-one 

Related news

Determination of viridicatin (cas 129-24-8) inPenicillium cyclopiumby Capillary Gas Chromatography09/28/2019

A sensitive gas chromatographic method for the determination of the quinoline alkaloid viridicatin, a fungal metabolite isolated from severalPenicilliumspecies and presumably a biogenetic precursor to naturally occurring diazepam-like 1,4-benzo-diazepines, has been developed. Prior to conversion...detailed

Viridicatol and viridicatin (cas 129-24-8) isolated from a shark-gill-derived fungus Penicilliumpolonicum AP2T1 as MMP-2 and MMP-9 inhibitors in HT1080 cells by MAPKs signaling pathway and docking studies09/27/2019

Matrix metalloproteinases (MMPs), the key enzymes in extracellular matrix degradation, seemed to increase in tumorigenesis, which has a relationship with metastasis and invasions. In this study, we investigated the MMP inhibitory effect of viridicatol and viridicatin, two compounds extracted fro...detailed

Pinacol Rearrangement of 3,4‐Dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones: An Alternative Pathway to viridicatin (cas 129-24-8) Alkaloids and Their Analogs09/26/2019

3‐Alkyl/aryl‐3‐hydroxyquinoline‐2,4‐diones were reduced with NaBH4 to give cis‐3‐alkyl/aryl‐3,4‐dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H2SO4, resulting in 4‐alkyl/aryl‐3‐hydroxyquinolin‐2(1...detailed

Ring‐Expansion Reaction of Isatins with Ethyl Diazoacetate Catalyzed by Dirhodium(II)/DBU Metal‐Organic System: En Route to viridicatin (cas 129-24-8) Alkaloids09/25/2019

We present here the NHC‐dirhodium(II)/DBU‐catalyzed ring expansion reaction of isatins with ethyl diazoacetate. This new one‐pot protocol yields the ethyl 3‐hydroxy‐2(1H)‐oxoquinoline‐4‐carboxylate core, regioselectively and in good to excellent yields. A DFT mechanistic study indicates ...detailed

Relevant academic research and scientific papers

Synthesis and Mechanistic Insights of the Formation of 3-Hydroxyquinolin-2-ones including Viridicatin from 2-Chloro- N,3-diaryloxirane-2-carboxamides under Acid-Catalyzed Rearrangements

N-Benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, easily obtained from aromatic aldehydes and anilides of dichloroacetic acid under Darzens condensation conditions, proved to be excellent starting compounds for the synthesis of 3-hydroxyindolin-2-ones, cyclohepto[b]pyrrole-2,3-diones, and 1-azaspiro[4.5]deca-3,6,9-triene-2-ones via the C(sp2)-C(sp2) bond formation in the first case and C(sp2)-C(sp3) bond formation in the second and third cases. Under optimized reaction conditions, 3-hydroxyindolin-2-ones are obtained in a one-pot process, which involves the treatment of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides with CF3CO2H or AcOH/H2SO4. In the case of intramolecular cyclization, the detailed reaction channels depend strongly on the substituents present in the anilide component and in the aromatic ring of the aldehyde component of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, as well as the temperature and duration of the reaction. A combined experimental and DFT mechanistic study of the formation of 1-benzyl-3-hydroxy-4-arylquinolin-2(1H)-ones showed that there are three competing reaction channels: (a) ring-closure via the ipso site, (b) ring-closure via the 1,2-Cl shift, and (c) ring-closure via the ortho site. Such mechanistic insights enabled an effective one-pot gram-scale synthesis of viridicatin from benzaldehyde and 2,2-dichloro-N-(4-methoxybenzyl)-N-phenylacetamide.

Harnessing the Substrate Promiscuity of Dioxygenase AsqJ and Developing Efficient Chemoenzymatic Synthesis for Quinolones

Nature has developed complexity-generating reactions within natural product biosynthetic pathways. However, direct utilization of these pathways to prepare compound libraries remains challenging because of limited substrate scopes, involvement of multiple-step reactions, and moderate robustness of these sophisticated enzymatic transformations. Synthetic chemistry offers an alternative approach to prepare natural product analogues. However, because of complex and diverse functional groups appended on the targeted molecules, dedicated design and development of synthetic strategies are typically required. Herein, by leveraging the power of chemoenzymatic synthesis, we report an approach to bridge the gap between biological and synthetic strategies in the preparation of quinolone alkaloid analogues. Leading byin silicoanalysis, the predicted substrate analogues were chemically synthesized. The AsqJ-catalyzed asymmetric epoxidation of these substrate analogues was followed by a Lewis acid-triggered ring contraction to complete the viridicatin formation. We evaluated the robustness of this method in gram-scale reactions. Lastly, through chemoenzymatic cascades, a library of quinolone alkaloids is effectively prepared.

Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones

Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.

Novel quinolone-based potent and selective HDAC6 inhibitors: Synthesis, molecular modeling studies and biological investigation

In this work we describe the synthesis of potent and selective quinolone-based histone deacetylase 6 (HDAC6) inhibitors. The quinolone moiety has been exploited as an innovative bioactive cap-group for HDAC6 inhibition; its synthesis was achieved by applying a multicomponent reaction. The optimization of potency and selectivity of these products was performed by employing computational studies which led to the discovery of the diethylaminomethyl derivatives 7g and 7k as the most promising hit molecules. These compounds were investigated in cellular studies to evaluate their anticancer effect against colon (HCT-116) and histiocytic lymphoma (U9347) cancer cells, showing good to excellent potency, leading to tumor cell death by apoptosis induction. The small molecules 7a, 7g and 7k were able to strongly inhibit the cytoplasmic and slightly the nuclear HDAC enzymes, increasing the acetylation of tubulin and of the lysine 9 and 14 of histone 3, respectively. Compound 7g was also able to increase Hsp90 acetylation levels in HCT-116 cells, thus further supporting its HDAC6 inhibitory profile. Cytotoxicity and mutagenicity assays of these molecules showed a safe profile; moreover, the HPLC analysis of compound 7k revealed good solubility and stability profile.

Regioselective Ring Expansion of Isatins with in Situ Generated α-Aryldiazomethanes: Direct Access to Viridicatin Alkaloids

A novel efficient one-pot regioselective ring-expansion reaction of isatins with in situ generated α-aryl/heteroaryldiazomethanes for the construction of viridicatin alkaloids has been described under metal-free conditions. The utility of this protocol is further demonstrated in the synthesis of naturally occurring viridicatin, viridicatol, and substituted 3-O-methyl viridicatin and their scale up.

Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.

THERAPEUTIC HYDROXYQUINOLONES

The invention provides compounds of formula (I) and salts thereof wherein R4-R8 have any of the meanings defined in the specification, as well as pharmaceutical compositions comprising the compounds or salts and methods for their use in therapy. The compounds have useful antiviral properties.

Pinacol rearrangement of 3,4-dihydro-3,4-dihydroxyquinolin-2(1H)-ones: An alternative pathway to viridicatin alkaloids and their analogs

3-Alkyl/aryl-3-hydroxyquinoline-2,4-diones were reduced with NaBH 4 to give cis-3-alkyl/aryl-3,4-dihydro-3,4-dihydroxyquinolin-2(1H)- ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H2SOs

Ring-expansion reaction of isatins with ethyl diazoacetate catalyzed by dirhodium(II)/DBU metal-organic system: En route to viridicatin alkaloids

We present here the NHC-dirhodium(II)/DBU-catalyzed ring expansion reaction of isatins with ethyl diazoacetate. This new one-pot protocol yields the ethyl 3-hydroxy-2(1H)-oxoquinoline-4-carboxylate core, regioselectively and in good to excellent yields. A DFT mechanistic study indicates metallocarbene formation between the 3-hydroxyindole-diazo intermediate and the dirhodium(II) complex to be the rate-limiting step of the reaction. The synthesized ethyl 3-hydroxy-2(1H)-oxoquinoline-4-carboxylate core could be readily converted to viridicatin alkaloids, in yields up to 80 % by a microwave-assisted Suzuki-Miyaura cross coupling of the 3-hydroxy-4-bromoquinolin-2(1H)-one with arylboronic acid. Copyright

3-Hydroxyquinolin-2(1H)-ones as inhibitors of influenza A endonuclease

Several 3-hydroxyquinolin-2(1H)-ones derivatives were synthesized and evaluated as inhibitors of 2009 pandemic H1N1 influenza A endonuclease. All five of the monobrominated 3-hydroxyquinolin(1H)-2-ones derivatives were synthesized. Suzuki-coupling of p-fluorophenylboronic acid with each of these brominated derivatives provided the respective p-fluorophenyl 3-hydroxyquinolin(1H)-2-ones. In addition to 3-hydroxyquinolin-2(1H)-one, its 4-methyl, 4-phenyl, 4-methyl-7-(p-fluorophenyl), and 4-phenyl-7-(p-fluorophenyl) derivatives were also synthesized. Comparative studies on their relative activity revealed that both 6- and 7-(p-fluorophenyl)-3-hydroxyquinolin-2(1H)- one are among the more potent inhibitors of H1N1 influenza A endonuclease. An X-ray crystal structure of 7-(p-fluorophenyl)-3-hydroxyquinolin-2(1H)-one complexed to the influenza endonuclease revealed that this molecule chelates to two metal ions at the active site of the enzyme.