53772-33-1

Usage

Uses

2-BroMo-1,4-diMethoxy-3-Methyl-naphthalene is used in the preparation of vitamin K2.

InChI:InChI=1/C13H13BrO2/c1-8-11(14)13(16-3)10-7-5-4-6-9(10)12(8)15-2/h4-7H,1-3H3

Upstream product

• 39055-47-5 2-bromo-3-methylnaphthohydroquinone 
• 77-78-1 dimethyl sulfate 
• 53772-19-3 1,4-dimethoxy-2-methylnaphthalene 
• 3129-39-3 2-bromo-3-methyl-[1,4]naphthoquinone 
• 481-85-6 2-methyl-1,4-naphthohydroquinone 
• 58-27-5 menadione 

Downstream Products

• 73875-18-0 (2′E)-2-(3′-methyl-4′-phenylsulfonylbut-2′-enyl)-1,4-dimethoxy-3-methylnaphthalene 
• 3129-39-3 2-bromo-3-methyl-[1,4]naphthoquinone 
• 64449-33-8 2-allyl-3-methyl-1,4-naphthoquinone 
• 21884-42-4 chlorobiumquinone 
• 17579-92-9 2-benzoyl-3-methylnaphthalene-1,4-dione 
• 84-81-1 farnoquinone 
• 46492-08-4 benz[g]isoquinoline-5,10-dione 

Relevant academic research and scientific papers

Synthesis and protein conjugation studies of vitamin K analogues

Two vitamin K analogues bearing a carboxylic acid side chain (9a and 9b) have been synthesised and coupled to N-acetyl-Gly-l-Lys methyl ester, lysozyme and bovine serum albumin (BSA) as a first step to the development of an ELISA-based method for the detection of vitamin K. The protein conjugates have been characterised by ESMS and LC-MS. Two vitamin K analogues bearing a carboxylic acid side chain (9a and its deuterated analogue 9b) were each synthesised in six steps from commercially available menadione. Analogue 9b was conjugated to lysozyme and bovine serum albumin (BSA) using EDCI/HOBT and by prior formation of its activated succinimidyl ester 11. Quantification of the thus formed conjugates by ESMS and LC-MS revealed that the number of equivalents of the analogue used in the couplings systematically controls the number of analogues that conjugate to the protein.

Novel method for synthesizing vitamin K2

The invention discloses a novel method for synthesizing vitamin K2. According to the method, the compound shown in the formula 4 with a brand-new structure is used as an intermediate, so that the vitamin K2 can be simply and safely synthesized at high yield. The method disclosed by the invention is beneficial to industrial production of the vitamin K2.

Synergistic factors ensue high expediency in the synthesis of menaquinone [K2] analogue MK-6: Application to access an efficient one-pot protocol to MK-9

Here we report a practical and efficient method for the synthesis of menaquinone vitamin (K2) analog MK-6 in all trans forms through “1 + 5 convergent synthetic approach” of pentaprenyl chloride with monoprenyl menadione derivative. In the synergistic factors, less efficient leaving group/more efficient nucleophile (Cl) in the substrate makes it more prominent reaction by eliminating all Sn2’ side reaction products. Further, the addition of acetic acid in the last step (desulfonation) of reaction sequence removes the limitations of the reactions in terms of cyclized side product (multiple reactions of pentaprenyl alcohol with Et3B), byproduct (Et3B, incendiary compound) formations and their interruption in the tricky purification processes. The utility of this method was further extended to find an efficient one-pot synthesis to MK-9 to the gram scale synthesis. This approach is economical and efficient and avoids the awkward chromatographic separation processes.

Synthesis and antitubercular activity of 1- and 3-substituted benzo[: G] isoquinoline-5,10-diones

In this study, a small library of twenty benzo[g]isoquinoline-5,10-diones were synthesized in a novel straightforward approach, starting from 2-methyl-1,4-naphthoquinone (vitamin K). An intramolecular Heck reaction of a N-vinylacetamide was a crucial step in the synthetic route, at which the combination of cesium carbonate and a bulky, electron rich trialkylphosphine (tBuCy2P.HBF4) provided high 6-endo-trig selectivity. The anti-tubercular activity against Mycobacterium tuberculosis H37Ra and acute cytotoxicity against J774 A.1 macrophages were studied. From the structure activity relationship, it could be derived that in general the substitution of position 3 yielded analogs with a higher antitubercular potency. Among these, two analogs, 27a and 27b, showed remarkable activity with minimal inhibition concentrations of respectively 28.92 μM and 1.05 μM, and acute cytotoxic concentrations of >128 μM and 34.85 μM. In addition, the analogs and their possible metabolites were evaluated using a Vitotox assay to study the possibility of genotoxicity. Results indicated that none of the evaluated analogs and their possible metabolites showed early signs of genotoxicity.

Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis

Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time.

Redox Polypharmacology as an Emerging Strategy to Combat Malarial Parasites

3-Benzylmenadiones are potent antimalarial agents that are thought to act through their 3-benzoylmenadione metabolites as redox cyclers of two essential targets: the NADPH-dependent glutathione reductases (GRs) of Plasmodium-parasitized erythrocytes and m

Stereoselective heck reactions with vinyl sulfoxides, sulfides and sulfones

We report the Heck cross-coupling of notoriously unreactive, but synthetically valuable olefins: vinyl sulfoxides, vinyl sulfones, and vinyl sulfides. Key findings include the importance of the sterically hindered (tri-tert-butyl)phosphine ligand and the unique effectiveness of triethylamine as the base. The method is general, E-selective, and can be used to synthesize disubstituted or trisubstituted olefins through simple adjustments of stoichiometry. Copyright

Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones - A new strategy to combat malarial parasites

Our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen Plasmodium falciparum in culture and a

Antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum

Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (FeIII)protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggesting a mode of action distinct from chloroquine mechanism.

2,3-Dimethoxy-5-methyl-1,4-benzoquinones and 2-methyl-1,4-naphthoquinones: Glycation inhibitors with lipid peroxidation activity

Anti-glycation activity of our anti-oxidant quinone library was measured and several 2,3-dimethoxy-5-methyl-1,4-benzoquinones and 2-methyl-1,4- naphthoquinones were identified as novel inhibitors of glycation, of which 2,3-dimethoxy-5-methyl-1,4-benzoquinones 13b is the most potent glycation inhibitor with around 50 μM of the IC50 value.