19040-71-2

Usage

Uses

Used in Pharmaceutical Industry:
4-(chloromethyl)-7,8-dihydroxy-2-benzopyrone is used as a key intermediate for the synthesis of daphnetin derivatives, which are known for their potent antioxidant properties. These derivatives have potential applications in the development of new drugs targeting various diseases and conditions where oxidative stress plays a significant role.
Used in Chemical Synthesis:
In the field of chemical synthesis, 4-(chloromethyl)-7,8-dihydroxy-2-benzopyrone serves as a versatile building block for the creation of a wide range of chemical compounds. Its unique structure allows for further functionalization and modification, making it a valuable starting material for the development of new molecules with diverse applications.
Used in Research and Development:
4-(chloromethyl)-7,8-dihydroxy-2-benzopyrone is also utilized in research and development settings, where it can be employed to study the structure-activity relationships of various chemical compounds. Its unique properties make it an interesting subject for investigation, potentially leading to the discovery of new compounds with novel applications.

InChI:InChI=1/C10H7ClO4/c11-4-5-3-8(13)15-10-6(5)1-2-7(12)9(10)14/h1-3,12,14H,4H2

Upstream product

• 638-07-3 ethyl (2-chloroaceto)acetate 
• 87-66-1 2-hydroxyresorcinol 
• 3153-36-4 4-chloro-butyric acid ethyl ester 
• 32807-28-6 Methyl 4-chloroacetoacetate 
• 525-52-0 pyrogallol triacetate 

Downstream Products

• 844828-43-9 7,8-dihydroxy-4-(morpholin-4-ylmethyl)chromen-2-one 
• 1262217-50-4 4-((N,N-diphenylamino)methyl)-7,8-dihydroxy-2H-chromen-2-one 
• 859129-74-1 4-(4-(4-fluorophenyl)piperazin-1-ylmethyl)-7,8-dihydroxy-2H-chromen-2-one 
• 1447735-18-3 4,4'-(ethane-1,2-diylbis(phenylazanediyl))bis(methylene)bis(7,8-dihydroxy-2H-chromen-2-one) 
• 877800-14-1 4-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-7,8-dihydroxy-2H-chromen-2-one 
• 443650-48-4 7,8-dihydroxy-4-hydroxymethyl-2H-chromen-2-one 

Relevant academic research and scientific papers

Expeditious Pechmann condensation by using biodegradable cellulose sulfuric acid as a solid acid catalyst

A facile synthesis of coumarins was performed in excellent yields via Pechmann condensation by using different type of phenols and ethylacetoacetates under solvent-free media using both conventional method and microwave irradiation in short reaction times is described. The reaction workup is very simple, and the catalyst can be easily separated from the reaction mixture and reused several times in subsequent reactions. Copyright

Zirconyl chloride: A useful catalyst in the Pechmann coumarin synthesis

Coumarin derivatives were prepared using zirconyl chloride octahydrate (1%) as a Pechmann catalyst, either neat or in some cases employing small volumes of ethanol as solvent. As result of this work, coumarins were obtained in moderate to good yields. Georg Thieme Verlag Stuttgart.

Dipyridine cobalt chloride: A novel catalyst for the synthesis of coumarins via Pechmann condensation

Dipyridine cobalt chloride is a novel catalyst for the Pechmann condensation involving different phenols and ethylacetoacetate under solvent-free conditions using both conventional methods and microwave irradiation. It gives the corresponding coumarins in excellent yields with high purity. The catalyst is thermally stable, inexpensive and recyclable. A faster reaction and higher yields compared to the conventional method and no side products were identified using microwave irradiation. In this reaction, electron releasing groups on the phenol ring shown more reactivity and gave high yields than simple phenol. These products were identified by 1H NMR, 13C NMR, MS, IR and elemental analysis.

Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe2+/Cu2+ Chelator in Cell and Animal Models of Parkinson’s Disease

Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson’s disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ～ Fe2+ > Zn2+ > Fe3+. No binding capacity was detected for Hg2+, Co2+, Ca2+, Mn2+, Mg2+, Ni2+, Pb2+, or Cd2+. DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY581/591. DHC12 also blocked the decrease in mitochondrial membrane potential, detected by tetramethylrhodamine distribution. DHC12 inhibited MAO-A and MAO-B activity. Oral administration of DHC12 to mice (0.25 mg/kg body weight) protected substantia nigra pars compacta (SNpc) neurons against MPTP-induced death. Taken together, our results support the concept that DHC12 is a mitochondrial-targeted neuroprotective iron-copper chelator and MAO-B inhibitor with potent antioxidant and mitochondria protective activities. Oral administration of low doses of DHC12 is a promising therapeutic strategy for the treatment of diseases with a mitochondrial iron accumulation component, such as PD.

Sulfated zirconia, a mild alternative to mineral acids in the synthesis of hydroxycoumarins

Sulfated zirconia (1%) was employed as Pechmann's catalyst without solvent or in some cases using a small amount of ethanol to obtain coumarins in moderate to good yields. With this procedure, no significant acidic waste was obtained and an environmental friendly alternative to obtain coumarins is provided.

Theoretical and experimental investigation of NMR, IR and UV-visible spectra of hydroxyl-substituted-4-chloromethylcoumarin derivatives

UV-Visible, FTIR and NMR experimental and theoretical spectral results have been compared for five substituted-4-chloromethylcoumarin derivatives (6-OH, 7-OH, 6,7-di-OH, 7,8-di-OH and 5,7-di-OH-substituted-4-chloromethylcoumarins). The theoretical investigation was conducted using density functional theory (DFT), namely the M06-2X functional form with 6-311+G(2df,2p) basis set. The 13C-NMR and 1H-NMR chemical shifts, vibrational spectra and molecular orbitals of the excited states were calculated based on their optimized geometries. The calculated values were found to have close agreement with the experimental values. The theoretical data are useful and could be important in the proper selection of compounds as intermediates for different chemical applications and modifications.

Synthesis and structure-activity relationship of coumarins as potent Mcl-1 inhibitors for cancer treatment

Myeloid cell leukemia-1 (Mcl-1) is a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to their resistance to current chemotherapeutics. In this study, more than thirty coumarin derivatives with different substituents were designed and synthesized, and their Mcl-1 inhibitory activities evaluated using a fluorescence polarization-based binding assay. The results showed that the catechol group was a key constituent for Mcl-1 inhibitory activity of the coumarins, and methylation of the catechol group led to decreased inhibitory activity. The introduction of a hydrophobic electron-withdrawing group at the C-4 position of 6,7-dihydroxycoumarin, enhanced Mcl-1 inhibitory capacity, and a hydrophilic group in this position was unbeneficial to the inhibitory potency. In addition, the introduction of a nitrogen-containing group to the C-5 or C-8 position, which allowed an intramolecular hydrogen bond, was also unfavorable for Mcl-1 inhibition. Among all coumarins tested, 4-trifluoromethyl-6,7-dihydroxycoumarin (Cpd 4) displayed the most potent inhibitory activity towards Mcl-1 (Ki = 0.21 ± 0.02 μM, IC50 = 1.21 ± 0.56 μM, respectively), for which the beneficial effect on taxol resistance was also validated in A549 cells. A strong interaction between Cpd 4 and Mcl-1 in docking simulations further supported the observed potent Mcl-1 inhibition ability of Cpd 4. 3D-QSAR analysis of all tested coumarin derivatives further provides new insights into the relationships linking the inhibitory effects on Mcl-1 and the steric-electrostatic properties of coumarins. These findings could be of great value for medicinal chemists for the design and development of more potent Mcl-1 inhibitors for biomedical applications.

Coumarin-Caged Compounds of 1-Naphthaleneacetic Acid as Light-Responsive Controlled-Release Plant Root Stimulators

Six coumarin-caged compounds of 1-naphthaleneacetic acid (NAA) comprising different substituents on the coumarin moiety were synthesized and evaluated for their photophysical and chemical properties as light-responsive controlled-release plant root stimulators. The 1H NMR and HPLC techniques were used to verify the release of NAA from the caged compounds. After irradiation at 365 nm, the caged compounds exhibited the fastest release rate at t1/2 of 6.7 days and the slowest release rate at t1/2 of 73.7 days. Caged compounds at high concentrations (10-5 and 10-6 M) significantly stimulate secondary root germination while free NAA at the same level is toxic and leads to inhibition of secondary root germination. The cytotoxicity of the caged compounds against fibroblasts and vero cells were evaluated, and the results suggested that, at 10-5-10-6 M, caged compounds exhibited no significant cytotoxicity to the cells. Thus, the caged compounds of NAA in this study could be of great benefit as efficient agrochemicals.

Synthesis and structure-activity relationship of daphnetin derivatives as potent antioxidant agents

In this study, daphnetin 1 was chosen as the lead compound, and C-3 or C-4-substituted daphnetins were designed and synthesized to explore the potential relationship between the antioxidant activities and the chemical structures of daphnetin derivatives. The antioxidant activities of the generated compounds were evaluated utilizing the free radical scavenging effect on 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis-(3-ethylbenzthiazoline-6-sulfonate) cation, and the ferric reducing power assays, and were then compared with those of the standard antioxidant Trolox. The results showed that the catechol group was the key pharmacophore for the antioxidant activity of the daphnetins. The introduction of an electron-withdrawing hydrophilic group at the C-4 position of daphnetin enhanced the antioxidative capacity, but this trend was not observed for C-3 substitution. In addition, introduction of a a hydrophobic phenyl group exerted negative effects on the antioxidant activity in both the C-3 and C-4 substitutions. Among all of the derivatives tested, the most powerful antioxidant was 4-carboxymethyl daphnetin (compound 9), for which the strongest antioxidant activity was observed in all of the assays. In addition, compound 9 also displayed strong pharmaceutical properties in the form of metabolic stability. To summarize, compound 9 holds great potential to be developed as an antioxidant agent with excellent antioxidant activity and proper pharmacokinetic behavior.

Gastroprotective activity of synthetic coumarins: Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors

Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20?mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole at 20?mg/kg and reducing gastric lesions by 75 and 76%, respectively. Then, in a second experiment, compounds 6 and 10 were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin 6, the protective effect was reduced by pre-treatment of the mice with N-ethylmaleimide and l-NAME suggesting that sulfhydryl compounds and endogenous nitric oxide are involved in its gastroprotective activity. While for coumarin 10 the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.