15116-11-7Relevant articles and documents
Synthesis, inhibitory activity and in silico docking of dual COX/5-LOX inhibitors with quinone and resorcinol core
Sisa, Miroslav,Dvorakova, Marcela,Temml, Veronika,Jarosova, Veronika,Vanek, Tomas,Landa, Premysl
, (2020/07/31)
Based on the significant anti-inflammatory activity of natural quinone primin (5a), series of 1,4-benzoquinones, hydroquinones, and related resorcinols were designed, synthesized, characterized and tested for their ability to inhibit the activity of cyclooxygenase (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) enzymes. Structural modifications resulted in the identification of two compounds 5b (2-methoxy-6-undecyl-1,4-benzoquinone) and 6b (2-methoxy-6-undecyl-1,4-hydroquinone) as potent dual COX/5-LOX inhibitors. The IC50 values evaluated in vitro using enzymatic assay were for compound 5b IC50 = 1.07, 0.57, and 0.34 μM and for compound 6b IC50 = 1.07, 0.55, and 0.28 μM for COX-1, COX-2, and 5-LOX enzyme, respectively. In addition, compound 6d was identified as the most potent 5-LOX inhibitor (IC50 = 0.14 μM; reference inhibitor zileuton IC50 = 0.66 μM) from the tested compounds while its inhibitory potential against COX enzymes (IC50 = 2.65 and 2.71 μM for COX-1 and COX-2, respectively) was comparable with the reference inhibitor ibuprofen (IC50 = 4.50 and 2.46 μM, respectively). The most important structural modification leading to increased inhibitory activity towards both COXs and 5-LOX was the elongation of alkyl chain in position 6 from 5 to 11 carbons. Moreover, the monoacetylation in ortho position of bromo-hydroquinone 13 led to the discovery of potent (IC50 = 0.17 μM) 5-LOX inhibitor 17 (2-bromo-6-methoxy-1,4-benzoquinone) while bromination stabilized the hydroquinone form. Docking analysis revealed the interaction of compounds with Tyr355 and Arg120 in the catalytic site of COX enzymes, while the hydrophobic parts of the molecules filled the hydrophobic substrate channel leading up to Tyr385. In the allosteric catalytic site of 5-LOX, compounds bound to Tyr142 and formed aromatic interactions with Arg138. Taken together, we identified optimal alkyl chain length for dual COX/5-LOX inhibition and investigated other structural modifications influencing COX and 5-LOX inhibitory activity.
Synthesis of the antibacterial benzoquinone primin and its water-soluble analogue, primin acid
Bhattacharya, Asish K.,Kaur, Tanpreet,Ganesh, Krishna N.
supporting information; experimental part, p. 1141 - 1144 (2010/05/19)
The biologically active natural product, primin and its water-soluble acid analogue, primin acid are prepared in 34% and 25% overall yields, respectively, from a common intermediate using a Grignard reaction and a Johnson-Claisen rearrangement as the key
Ultrasound-assisted Wittig reaction: A short, efficient synthesis of 2-methoxy-6-alkyl-1,4-benzoquinones
Wu, Li-Qiang,Yang, Chun-Guang,Yang, Li-Ming,Yang, Li-Juan
experimental part, p. 47 - 50 (2010/04/05)
A short, efficient synthesis of 2-methoxy-6-alkyl-1,4-benzoquinones is described. Ultrasound-assisted Wittig reaction of alkyltriphenyl phosphonium bromides with o-vanillin in basic aqueous conditions followed by reduction with Na/n-BuOH gave 2-methoxy-6-alkylphenols. Oxidation of 2-methoxy-6-alkylphenols with Fremy's salt produced the title compounds.
Microwave-mediated claisen rearrangement followed by phenol oxidation: A simple route to naturally occurring 1,4-benzoquinones. The first syntheses of verapliquinones A and B and panicein A
Davis, Christopher J.,Hurst, Timothy E.,Jacob, Aouregan M.,Moody, Christopher J.
, p. 4414 - 4422 (2007/10/03)
The naturally occurring 1,4-benzoquinones 2-methoxy-6-propyl-1,4- benzoquinone (1), 2-methoxy-6-pentyl-1,4-benzoquinone (primin 2), 2-methoxy-6-pentadecyl-1,4-benzoquinone (3), 2-methoxy-6-heptadecyl-l,4- benzoquinone (dihydroirisquinone, pallasone B; 4) were synthesized by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 10, followed by hydrogenation of the side chain alkene, and oxidation to the quinone. The Claisen-based methodology was extended to the first synthesis of the marine benzoquinones verapliquinones A and B (5 and 6), and panicein A (7). Isoarnebifuranone (9) was also synthesized by a similar strategy.
The Claisen rearrangement followed by phenol oxidation: A simple route to naturally occurring benzoquinones including an ansa-bridged derivative related to the ansamycin antibiotics
Davis, Christopher J.,Moody, Christopher J.
, p. 1874 - 1876 (2007/10/03)
The naturally occurring benzoquinones primin 1 and pallasone B 2 were synthesised by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 4, followed by hydrogenation of the side chain alkene, and oxidation to the quinon
Isolation, Synthesis, Structure-Activity Relationships of Bioactive Benzoquinones from Miconia lepidota from the Suriname Rainforest
Gunatilaka, A. A. Leslie,Berger, John M.,Evans, Randy,Miller, James S.,Wisse, Jan H.,Neddermann, Kim M.,Bursuker, Isia,Kingston, David G. I.
, p. 2 - 5 (2007/10/03)
Bioactivity-directed fractionation of an EtOAc extract from the leaves of Miconia lepidota afforded the two benzoquinones 2-methoxy-6-heptyl-1,4-benzoquinone (1) and 2-methoxy-6-pentyl-1,4-benzoquinone (primin) (2). This is the first reported isolation of
New syntheses of the benzoquinone primin and its water-soluble analog primin acid via Heck reactions
Mabic,Vaysse,Benezra,Lepoittevin
, p. 1127 - 1134 (2007/10/03)
The syntheses of primin, 2-methoxy-6-pentylbenzoquinone (1), a major allergen of Primula obconica, and its water-soluble acid analog primin acid (2) are reported. The key steps were ortho-lithiation reactions of protected hydroquinones, palladium coupling (Heck) reactions, and salcomine-catalyzed oxidations of phenols to quinones.
Synthesis of Side-Chain-Modified Analogues of the Allergen Primin
Koenig, Wilfried A.,Faasch, Holger,Heitsch, Holger,Colberg, Cornelia,Hausen, Bjoern M.
, p. 387 - 393 (2007/10/02)
Benzoquinones such as primin (2-methoxy-6-pentyl-1,4-benzoquinone) from Primula obconica HANCE (Primulaceae) are known to be strong sensitizers and thus the source of severe allergic contact dermatitis (cell-mediated type of allergy).In order to determine
