- One-Pot Biocatalytic In Vivo Methylation-Hydroamination of Bioderived Lignin Monomers to Generate a Key Precursor to L-DOPA
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Electron-rich phenolic substrates can be derived from the depolymerisation of lignin feedstocks. Direct biotransformations of the hydroxycinnamic acid monomers obtained can be exploited to produce high-value chemicals, such as α-amino acids, however the reaction is often hampered by the chemical autooxidation in alkaline or harsh reaction media. Regioselective O-methyltransferases (OMTs) are ubiquitous enzymes in natural secondary metabolic pathways utilising an expensive co-substrate S-adenosyl-l-methionine (SAM) as the methylating reagent altering the physicochemical properties of the hydroxycinnamic acids. In this study, we engineered an OMT to accept a variety of electron-rich phenolic substrates, modified a commercial E. coli strain BL21 (DE3) to regenerate SAM in vivo, and combined it with an engineered ammonia lyase to partake in a one-pot, two whole cell enzyme cascade to produce the l-DOPA precursor l-veratrylglycine from lignin-derived ferulic acid.
- Birmingham, William R.,Galman, James L.,Parmeggiani, Fabio,Seibt, Lisa,Turner, Nicholas J.
-
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- Biotechnological Potential of Eugenol and Thymol Derivatives Against Staphylococcus aureus from Bovine Mastitis
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Bovine mastitis is an infectious disease that affects the mammary gland of dairy cattle with considerable economic losses. Staphylococcus aureus is the main microorganism involved in this highly contagious process, and the treatment is only using antibiotics. Currently, the search for new treatment and/or compounds is still in need due to microbial resistance. In this work, we evaluated the potential of eugenol and thymol derivatives against S. aureus strains from bovine mastitis. On that purpose, nine derivatives were synthesized from eugenol and thymol (1–9), and tested against 15 strains of S. aureus from subclinical bovine mastitis. Initially, the strains were evaluated for the biofilm production profile, and those with strong adherence were selected to the antimicrobial sensitivity determination in the Minimum Inhibitory Concentration (MIC) assays. Herein the compounds toxicity was also evaluated by in silico analysis using Osiris DataWarrior software. The results showed that 60% of the strains were considered strongly adherent and three strains (S. aureus 4271, 4745 and 4746) were selected for the MIC tests. Among the nine eugenol and thymol derivatives tested, four were active against the evaluated strains (MIC = 32?μg?mL?1) within CLSI standard values. In silico analysis showed that all derivatives had cLopP ??4 and TPSA 140 ?2, and similar theoretical toxicity parameters to some antibiotics currently on the market. These molecules also showed negative drug-likeness values, pointing to the originality of these structures and theoretical feasibility on escaping of resistance mechanism and act against resistant strains. Thus, these eugenol derivatives may be considered as promising for the development of new treatments against bovine mastitis and future exploring on this purpose.
- Nunes, Daiana O. S.,Vinturelle, Rafaelle,Martins, Francislene J.,dos Santos, Thiago F.,Valverde, Alessandra Leda,Ribeiro, Carlos Magno R.,Castro, Helena C.,Folly, Evelize
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p. 1846 - 1855
(2021/04/29)
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- Nickel-catalyzed reductive deoxygenation of diverse C-O bond-bearing functional groups
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We report a catalytic method for the direct deoxygenation of various C-O bond-containing functional groups. Using a Ni(II) pre-catalyst and silane reducing agent, alcohols, epoxides, and ethers are reduced to the corresponding alkane. Unsaturated species including aldehydes and ketones are also deoxygenated via initial formation of an intermediate silylated alcohol. The reaction is chemoselective for C(sp3)-O bonds, leaving amines, anilines, aryl ethers, alkenes, and nitrogen-containing heterocycles untouched. Applications toward catalytic deuteration, benzyl ether deprotection, and the valorization of biomass-derived feedstocks demonstrate some of the practical aspects of this methodology.
- Cook, Adam,MacLean, Haydn,St. Onge, Piers,Newman, Stephen G.
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p. 13337 - 13347
(2021/11/20)
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- Nitration of methyl eugenol derived from clove oil
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No report is available in literature for the nitration of methyl eugenol. The main goal of this work is to find an efficient method for the synthesis of 5-nitro-methyl eugenol. 5-Nitro-methyl eugenol is of considerable importance in the production of other fine chemicals such as 5-amino-methyl eugenol for further chemical synthesis and has also possible to enhance its biological properties and other applications. The methyl eugenol can be prepared from methylation of eugenol which can be isolated from clove oil. In an attempt to synthesize nitro-methyl eugenol in high yield, three different nitration methods of methyl eugenol have been applied. Method (a) gave 5.97 %, (b) 84.37 % and (c) 11.40 %. Method (b) using a nitrating consisting mixture of HNO3 and H2SO4 under mild condition has been found to give 5-nitro-methyl eugenol in good yield.
- Sudarma,Shofiati,Darmayanti
-
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- Specific Residues Expand the Substrate Scope and Enhance the Regioselectivity of a Plant O-Methyltransferase
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An isoeugenol 4-O-methyltransferase (IeOMT), isolated from the plant Clarkia breweri, can be engineered to a caffeic acid 3-O-methyltransferase (CaOMT) by replacing three consecutive residues. Here we further investigated functions of these residues by constructing the triple mutant T133M/A134N/T135Q as well as single mutants of each residue. Phenolics with different chain lengths and different functional groups were investigated. The variant T133M improves the enzymatic activities against all tested substrates by providing beneficial interactions to residues which directly interact with the substrate. Mutant A134N significantly enhanced the regioselectivity. It is meta-selective or even specific against most of the tested substrates but para-specific towards 3,4-dihydroxybenzoic acid. The triple mutant T133M/A134N/T135Q benefits from these two mutations, which not only expand the substrate scope but also enhance the regioselectivity of IeOMT. On the basis of our work, regiospecific methylated phenolics can be produced in high purity by different IeOMT variants.
- Tang, Qingyun,Bornscheuer, Uwe T.,Pavlidis, Ioannis V.
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p. 3227 - 3233
(2019/07/04)
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- Design, synthesis and pharmacological evaluation of novel antiinflammatory and analgesic O-benzyloxime compounds derived from natural eugenol
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Background: A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.
- Da Silva, Rodrigo César,Veiga, Fabiano,Vilela, Fabiana Cardoso,Pereira, André Victor,Da Silva Cunha, Thayssa Tavares,Tesch, Roberta,Viegas, Claudio,Dias, Danielle Ferreira,Giusti-Paiva, Alexandre,Veloso, Marcia Paranho,Fraga, Carlos Alberto Manssour
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p. 1157 - 1166
(2019/10/28)
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- Stereoselective Synthesis of 1-Arylpropan-2-amines from Allylbenzenes through a Wacker-Tsuji Oxidation-Biotransamination Sequential Process
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Herein, a sequential and selective chemoenzymatic approach is described involving the metal-catalysed Wacker-Tsuji oxidation of allylbenzenes followed by the amine transaminase-catalysed biotransamination of the resulting 1-arylpropan-2-ones. Thus, a series of nine optically active 1-arylpropan-2-amines were obtained with good to very high conversions (74–92%) and excellent selectivities (>99% enantiomeric excess) in aqueous medium. The Wacker-Tsuji reaction has been exhaustively optimised searching for compatible conditions with the biotransamination experiments, using palladium(II) complexes as catalysts and iron(III) salts as terminal oxidants in aqueous media. The compatibility of palladium/iron systems for the chemical oxidation with commercially available and made in house amine transaminases was analysed, finding ideal conditions for the development of a general and stereoselective cascade sequence. Depending on the selectivity displayed by selected amine transaminase, it was possible to produce both 1-arylpropan-2-amines enantiomers under mild reaction conditions, compounds that present therapeutic properties or can be employed as synthetic intermediates of chiral drugs from the amphetamine family. (Figure presented.).
- González-Martínez, Daniel,Gotor, Vicente,Gotor-Fernández, Vicente
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p. 2582 - 2593
(2019/05/15)
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- Palladium-Catalyzed Oxidative Allylation of Sulfoxonium Ylides: Regioselective Synthesis of Conjugated Dienones
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The first examples of palladium-catalyzed allylic C-H oxidative allylation of sulfoxonium ylides to afford the corresponding conjugated dienones with moderate to good yields have been established. The features of this novel conversion include mild reaction conditions, wide substrate scope, and excellent regioselectivity.
- Li, Chunsheng,Li, Meng,Zhong, Wentao,Jin, Yangbin,Li, Jianxiao,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 872 - 875
(2019/05/16)
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- Free Radical Scavenging Activity of Essential Oil of Eugenia caryophylata from Amboina Island and Derivatives of Eugenol
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Essential oil from Eugenia caryophylata was normally used to heal many different deseaces. Various chemical compositions of essential oil distilled and steamed of Moluccas Eugenia caryophylata has been investigated by many different researchers. Even though an intensive research has been carried out of the local chemotypes, a very detail study has not been fully investigated to find out the complete chemical compounds from the plant essential oil and its content associated with their biological activities. In present paper, we assess the free radical scavenging of E. caryophylata collected from Moluccas islands, Indonesia. Essential oil was extracted from leaves, buds, and stems of plant by steam distillation and analyzed using GC-FID and GC-MS. The result showed that free radical activity of essential oil, main constituent and its derivatives were analized using in vitro method. Essential oil activity from stem obtained as (0.82±0.15 μg/mL) was higher than that from bud and leaf possessing both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and (2,2'-azino-bis-3-ethylbenzthizoline-6-sulphonic acid (ABTS) radical scavenging assays by sinergism of eugenol, eugenyl acetate, β-caryophylene and humulene. The activity of isoeugenol (2) (3.59±0.54 μM) and (5.0±0.53 μM) scavenging DPPH and ABTS, respectively, as derivatives eugenol was higher than (3), (4) and (5). Although (6) was active originally, it was inactive after conversion of the ester. While the change of the double bond of location to conjungation structure caused more activity scavenging radicals than the starting molecule.
- Julianus Sohilait, Hanoch,Kainama, Healthy
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p. 422 - 428
(2019/08/01)
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- Decarboxylative Olefination of Activated Aliphatic Acids Enabled by Dual Organophotoredox/Copper Catalysis
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Herein, we demonstrate a dual organophotoredox/copper catalytic strategy toward challenging decarboxylative olefination processes proceeding in high yields and selectivities. This operationally simple method uses photoactive organic molecules and Cu(II)-complexes as catalysts to provide rapid access to a wide variety of olefins from inexpensive synthetic and biomass-derived carboxylic acids under mild light-mediated conditions. Mechanistic investigations suggest that the reaction rate for this process is controlled solely by the incident photon flux.
- Tlahuext-Aca, Adrian,Candish, Lisa,Garza-Sanchez, R. Aleyda,Glorius, Frank
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p. 1715 - 1719
(2018/03/13)
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- Synthesis and biological activity of novel phenol-conjugates of isoxazolidines
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1,3-Dipolar cycloadditions of the phosphonylnitrone with selected allylbenzenes produced mixtures of diastereoisomeric (3-diethoxyphosphoryl)isoxazolidines with good trans/cis diastereoselectivities (d.e. 80%) and good to excellent overall yields. No inhibitory activity against a broad panel of DNA and RNA viruses was detected for (3-diethoxyphosphoryl)isoxazolidines at 250 μM. Isoxazolidines trans-3k : cis-3k (95: 5) slightly reduced human embryonic lung (HEL) cell viability (CC50 = 45 μM). Four out of ten isoxazolidines inhibited the growth of Staphylococcus epidermidis ATCC 12228 (up to 40% for the most active compound). They were also inhibitory against Staphylococcus aureus ATCC 6538 although inhibition did not exceeded 25%. None of the isoxazolidines affected Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 15442 growth.
- Piotrowska, Dorota G.,Wróblewski, Andrzej E.,Balzarini, Jan,Andrei, Graciela,Schols, Dominique,Snoeck, Robert,Felczak, Aleksandra,Wrońska, Natalia,Lisowska, Katarzyna,G?owacka, Iwona E.
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p. 1091 - 1100
(2017/08/01)
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- Palladium-catalyzed oxidative allylation of bis[(pinacolato)boryl]methane: Synthesis of homoallylic boronic esters
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A palladium-catalyzed oxidative allylation of bis[(pinacolato)boryl]methane to afford the corresponding homoallylic organoboronic esters with moderate to excellent yields is reported. This novel transformation provides an efficient strategy for the construction of homoallylic organoboronic esters in one step with a broad substrate scope. It is proposed that the palladium-catalyzed oxidative allylic C-H bond activation process may be involved in the catalytic cycle.
- Li, Chunsheng,Li, Meng,Li, Jianxiao,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 66 - 69
(2017/12/27)
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- Cu2O spheres as an efficient source of catalytic Cu(I) species for performing azide-alkyne click reactions
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We report herein the high yield synthesis of Cu2O spheres displaying well-defined shapes and monodisperse sizes that could be employed as the source of highly catalytic active Cu(I) species towards click reactions between several of alkynes and azides to produce a variety of 1,2,3-triazoles under ligand-free and ambient conditions (in an open reactor). The utilization of Cu2O spheres enabled superior performance as compared to a conventional protocol in which CuSO4is employed in combination with sodium ascorbate as the catalyst system. In addition, the compounds were obtained in synthetically useful yields, and seven of them have not been previously reported. We believe the results reported herein shed new insights into the optimization of activity and versatility of click reactions towards the synthesis of target molecules in environmentally friendly conditions.
- Rodrigues, Thenner S.,da Silva, Anderson G.M.,de Oliveira, Lucas C.,da Silva, Adalberto M.,Teixeira, Róbson R.,Camargo, Pedro H.C.
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supporting information
p. 590 - 595
(2017/01/16)
-
- Masked N-Heterocyclic Carbene-Catalyzed Alkylation of Phenols with Organic Carbonates
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An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2), was investigated as a “green” and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs.
- Lui, Matthew Y.,Yuen, Alexander K. L.,Masters, Anthony F.,Maschmeyer, Thomas
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p. 2312 - 2316
(2016/10/24)
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- A Facile, Convenient, and Green Route to (E)-Propenylbenzene Flavors and Fragrances by Alkene Isomerization
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(E)-Propenylbenzene flavors and fragrances can be made and isolated in high yield and selectivity by using bifunctional catalyst 1, and the heterogenized analogues. Multigram-scale reactions can be performed neat and the products isolated either by distillation, using homogeneous catalyst 1 (0.1-0.5 mol%, r.t., 10-45 min), or by decantation from heterogeneous catalysts PS-1 or PSL-1 (0.5 mol%, 70 °C, 24 h; catalyst separation and re-use shown for 3-4 cycles; 10 cycles using distilled eugenol feedstock). Both purified starting materials and essential oil feedstocks could be used. Z Isomers were present at very low levels (from 0.4% to less than 0.1%) in the products.
- Larsen, Casey R.,Paulson, Erik R.,Erdogan, Gulin,Grotjahn, Douglas B.
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supporting information
p. 2462 - 2466
(2015/10/19)
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- Total synthesis of (-)-Haouamine B pentaacetate and structural revision of haouamine B
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The enantiocontrolled total synthesis of (-)-haouamine B pentaacetate was accomplished via an optically active indane-fused β-lactam, which was prepared by a newly developed Friedel-Crafts reaction. Subsequent cleavage of the β-lactam and an intramolecular McMurry coupling reaction provided the core indane-fused tetrahydropyridine, which led to the elucidation of the structure, as proposed by Trauner and Zuba.
- Momoi, Yuichi,Okuyama, Kei-Ichiro,Toya, Hiroki,Sugimoto, Kenji,Okano, Kentaro,Tokuyama, Hidetoshi
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supporting information
p. 13215 - 13219
(2015/01/09)
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- Method for Allylating and Vinylating Aryl, Heteroaryl, Alkyl, and Alkene Halogenides Using Transition Metal Catalysis
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What is described is a process for preparing organic compounds of the general formula (I) R—R′??(I) by converting a corresponding compound of the general formula (II) R—X ??(II) in which X is fluorine, chlorine, bromine or iodine to an organomagnesium compound of the general formula (III) [M+]n[RmMgXkY1]??(III) wherein compounds of the formula (III) are reacted with a compound of the general formula (IV) characterized in that the reaction of (III) with (IV) is performed in the presence of a) catalytic amounts of an iron compound, based on the compound of the general formula (II), and optionally in the presence of b) a nitrogen-, oxygen- and/or phosphorus-containing additive in a catalytic or stoichiometric amount, based on the compound of the general formula (II).
- -
-
Paragraph 0062; 0063; 0064
(2013/07/25)
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- Sterically controlled alkylation of arenes through iridium-catalyzed C-H borylation
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Complementary chemistry: A one-pot method for the site-selective alkylation of arenes controlled by steric effects is reported. The process occurs through Ir-catalyzed C-H borylation, followed by Pd- or Ni-catalyzed coupling with alkyl electrophiles. This selectivity complements that of the typical Friedel-Crafts alkylation; meta-selective alkylation of a broad range of arenes with various electronic properties and functional groups occurs in good yield with high site selectivity. Copyright
- Robbins, Daniel W.,Hartwig, John F.
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p. 933 - 937
(2013/02/25)
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- Nickel-catalyzed reductive coupling of aryl halides with secondary alkyl bromides and allylic acetate
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A room-temperature Ni-catalyzed reductive method for the coupling of aryl bromides with secondary alkyl bromides has been developed, providing C(sp 2)-C(sp3) products in good to excellent yields. Slight modification of this protocol allows efficient coupling of activated aryl chlorides with cyclohexyl bromide and aryl bromides with allylic acetate.
- Wang, Shulin,Qian, Qun,Gong, Hegui
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supporting information; experimental part
p. 3352 - 3355
(2012/08/08)
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- Synthesis of isoquinoline alkaloid derivatives from eugenol
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Alkylation under phase-transfer catalysis conditions (18-crown-6/KOH) of eugenol was used for cyclocondensation with nitriles (Ritter reaction), the products of which were isoquinoline derivatives.
- Mikhailovskii,Surikova,Limanskii,Vakhrin
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experimental part
p. 285 - 287
(2012/09/07)
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- Synthesis of novel isoxazolines via 1,3-dipolar cycloaddition and evaluation of anti-stress activity
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We have synthesized a series of novel isoxazolines via 1,3-dipolar cycloaddition of in situ generated nitrile oxide from 2,4-dimethoxy benzaldoxime and naphthaldehyde oxime with 4-allyl-2-methoxyphenol derivatives. The synthesized compounds were evaluated for anti-stress activity in acute stress (AS) induced peripheral changes. Adult male Sprague-Dawley rats, subjected to AS, cause a significant increase in gastric ulceration, adrenal gland weight, plasma glucose, corticosterone levels, and creatine kinase activity. Compounds 3d, 3g, 5b, 5c, 5d, and 5g displayed most promising anti-stress effect by reverting these peripheral stress parameters at a dose of 40 mg/kg p.o.
- Maurya, Rakesh,Ahmad, Ausaf,Gupta, Prasoon,Chand, Kailash,Kumar, Manmeet,Jayendra,Rawat, Preeti,Rasheed, Naila,Palit, Gautam
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experimental part
p. 139 - 145
(2012/03/10)
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- Alkylphenol activity against candida spp. and microsporum canis: A focus on the antifungal activity of thymol, eugenol and o-methyl derivatives
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In recent years there has been an increasing search for new antifungal compounds due to the side effects of conventional antifungal drugs and fungal resistance. The aims of this study were to test in vitro the activity of thymol, eugenol, estragole and anethole and some O-methyl-derivatives (methylthymol and methyleugenol) against Candida spp. and Microsporum canis. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC). The minimum fungicidal concentrations (MFC) for both Candida spp. and M. canis were found by subculturing each fungal suspension on potato dextrose agar. Thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and griseofulvin respectively, presented the following MIC values against M. canis: 4.8-9.7; 78-150; 39; 78-150; 78-150; 19-39 μg/mL and 0.006-2.5 μg/mL. The MFC values for all compounds ranged from 9.7 to 31 μg/mL. Concerning Candida spp, thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and amphotericin, respectively, showed the following MIC values: 39; 620-1250; 150-620; 310-620; 620; 620-1250 and 0.25-2.0 μg/mL. The MFC values varied from 78 to 2500 μg/mL. All tested compounds thus showed in vitro antifungal activity against Candida spp. and M. canis. Therefore, further studies should be carried out to confirm the usefulness of these alkylphenols in vivo.
- Fontenelle, Raquel O.S.,Morais, Selene M.,Brito, Erika H.S.,Brilhante, Raimunda S.N.,Cordeiro, Rossana A.,Lima, Ynayara C.,Brasil, Nilce V.G.P.S.,Monteiro, Andre J.,Sidrim, Jose J.C.,Rocha, Marcos F.G.
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experimental part
p. 6422 - 6431
(2011/10/31)
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- Practical iron-catalyzed allylations of aryl grignard reagents
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An operationally simple iron-catalyzed reductive cross-coupling reaction between aryl halides and allyl electrophiles has been developed. The underlying domino process exhibits high versatility with respect to the allylic leaving group (acetate, tosylate, diethyl phosphate, methyl carbonate, trimethylsilanolate, methanethiolate, chloride, bromide) and high economic and environmental sustainability with respect to the catalyst system (0.2-5 mol% tris(acetylacetonato)iron(III), ligand-free) and reaction conditions (tetrahydrofuran, 0°C, 45 min).
- Mayer, Matthias,Czaplik, Waldemar M.,Von Wangelin, Axel Jacobi
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supporting information; experimental part
p. 2147 - 2152
(2010/12/18)
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- Substituted dihydronaphthalenes as efflux pump inhibitors of Staphylococcus aureus
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A new series of 3-(substituted-3,4-dihydronaphthyl)-2-propenoic acid amides has been prepared through convergent synthetic strategies and tested in combination with ciprofloxacin against NorA overexpressing Staphylococcus aureus 1199B as test strain for potentiating of the drug activity. Out of 24 compounds evaluated, 12 compounds potentiated the activity of ciprofloxacin and resulted in 2-16 fold reduction in the MIC (4-0.5 μg/mL) of the drug. The failure of these efflux pump inhibitors (EPIs) to potentiate the activity of ciprofloxacin when tested against NorA knock out S. aureus SA-K1758 established their identity as NorA inhibitors. The structure of all these newly synthesised compounds was confirmed by spectral data. The present communication describes the synthesis, bioevaluation, structure activity relationship and mechanism of action of these EPIs. Design and synthesis of new series of 3-(substituted 3,4-dihydronaphthyl)- propenoic acid amides as efflux pump inhibitors has resulted in the MIC reduction of ciprofloxacin.
- Thota, Niranjan,Reddy, Mallepally V.,Kumar, Ashwani,Khan, Inshad A.,Sangwan, Payare L.,Kalia, Nitin P.,Koul, Jawahir L.,Koul, Surrinder
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experimental part
p. 3607 - 3616
(2010/09/18)
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- Synthesis of aryl alkyl ethers by alkylation of phenols with quaternary ammonium salts
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Phenolic compounds can be efficiently O-methylated with tetramethylammonium chloride in diglyme or polyethyleneglycol (PEG) at temperatures of 150-160 °C and in the presence of either K2CO3 or NaOH. When applying benzyl-trimethylammonium chloride as a reagent, the benzylation and methylation of phenols occurs, with the benzylation product always predominating. With allyl-substituted phenols as substrates and using NaOH as a base it was possible to achieve both the alkylation and the double-bond isomerization of the allyl group to obtain (E/Z)-propenyl-substituted methyl and benzyl aryl ethers in a single preparative step.
- Maras, Nenad,Polanc, Slovenko,Kocevar, Marijan
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experimental part
p. 29 - 36
(2010/09/05)
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- Sodium dithionite initiated addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to allylaromatics. Facile synthesis of conjugated dienes substituted with terminal CF3 group
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Sodium dithionite effectively promotes the addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to the terminal double bond of allylbenzenes 1. The reactions proceeded in MeCN/H2O to give a 3:1 mole ratio of diastereoisomers of 1-(2-bromo-4-chloro-5,5,5-trifluoropentyl)benzenes 2 as the main products together with small amounts of its reductive debromination products 3. Total yields of 2 and 3 were dependent on the nature of the aromatic ring substituents in 1. Treatment of adducts 2 with DBU in refluxing hexanes resulted in double dehydrohalogenation affording, in good yields, conjugated dienes 4 (1,1,1-trifluoro-5-phenyl-2,4-pentadienes) terminated with the CF3 group at the one end and the phenyl group at the opposite end. These dienes were found to be sufficiently reactive to undergo Diels-Alder condensation with active dienophiles to give trifluoromethylated carbocycles. The reactions of CF3CHClBr with allylheterocycles were less successful and lead to low yields of mixtures of hardly separable compounds or to polymeric resins.
- Ignatowska, Jolanta,Dmowski, Wojciech
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p. 720 - 729
(2008/03/28)
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- Expeditious synthesis of bioactive allylphenol constituents of the genus Piper through a metal-free photoallylation procedure
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Nine bioactive allylphenol (anisole) derivatives (e.g. eugenol, safrole and asaricin) present in several plants of the genus Piper have been synthesized in medium to high yield via aryl cation intermediates. This expeditious metal-free procedure involves the irradiation of the corresponding chlorophenols or chloroanisoles in a polar solvent (MeCN or, better, TFE or aqueous acetonitrile) in the presence of allyltrimethylsilane. Estragole has also been synthesized starting from the corresponding fluoroderivative and diazonium salt, though in a lower yield. The Royal Society of Chemistry 2005.
- Protti, Stefano,Fagnoni, Maurizio,Albini, Angelo
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p. 2868 - 2871
(2007/10/03)
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- The sulfonation of methyl and prenyl ethers of naturally occurring phenols with trimethylsilylchlorosulfonate as sulfonating agent
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At room temperature trimethylsilylchlorosulfonate has been found to be an effective and a mild reagent for the nuclear sulfonation of some methyl and prenyl ethers of naturally occurring phenols.
- Petit, Philippe,Bourgeois, Paul
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p. 194 - 195
(2007/10/03)
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- Rhodium- and iridium-catalyzed allylation of electron-rich arenes with allyl tosylate
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The allylation of electron-rich arenes with allyl tosylate proceeded at 0°C in the presence of [Rh(nbd)(CH3CN)2]PF 6. Various oxygenated arenes were allylated with high para-selectivity in almost all cases. Especially in t
- Tsukada, Naofumi,Yagura, Yasushige,Sato, Tetsuo,Inoue, Yoshio
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p. 1431 - 1434
(2007/10/03)
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- Pd-Catalyzed Cross-Coupling of Haloarenes and Chloroarene-Cr(CO) 3 Complexes with Stabilized Vinyl- and Allylaluminium Reagents
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The palladium-catalyzed cross-coupling of intramolecularly stabilized divinyl- and diallylaluminium compounds 1 and 2 with haloarenes and chloroarene-Cr(CO)3 complexes has been studied. The coupling products were obtained in high yields (up to
- Schumann, Herbert,Kaufmann, Jens,Schmalz, Hans-Günther,B?ttcher, Andreas,Gotov, Battsengel
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p. 1783 - 1788
(2007/10/03)
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- Suppression of chemical mutagen-induced SOS response by alkylphenols from clove (Syzygium aromaticum) in the Salmonella typhimurium TA1535/pSK1002 umu test
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A methanol extract from clove (Syzygium aromaticum) showed a suppressive effect of the SOS-inducing activity on the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) in the Salmonella typhimurium TA1535/pSK1002 umu test. The methanol extract was re-extracted with hexane, dichloromethane, ethyl acetate, butanol, and water. The hexane fraction showed a suppressive effect. Suppressive compounds in the hexane fraction were isolated by silica gel column chromatography and identified as trans-isoeugenol (1) and eugenol (2) by GC, GC-MS, IR, and 1H and 13C NMR spectroscopy. Compounds 1 and 2 suppressed the furylfuramide-induced SOS response in the umu test. Compounds 1 and 2 suppressed 42.3 and 29.9% of the SOS-inducing activity at a concentration of 0.60 μmol/mL. These compounds were assayed with other mutagens, 4-nitroquinolin 1-oxide (4NQO) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). In addition, compounds 1 and 2 were assayed with aflatoxin B1 (AFB1) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing enzymes. These compounds showed suppressive effects of the SOS-inducing activity against furylfuramide, 4NQO, AFB1, and Trp-P-1. To research the structure-activity relationship, methyl esters of 1 and 2 (1Me and 2Me) and o-eugenol (3), as compounds similar to 2, were also assayed with all mutagens. Compounds 1Me, 2Me, and 3 showed weak suppressive effects of the SOS-inducing activity against furylfuramide.
- Miyazawa,Hisama
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p. 4019 - 4025
(2007/10/03)
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- Chemoselective O-methylation of phenols under non-aqueous condition
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Chemoselective O-methylation of substituted phenols takes place in dry. tetrahydrofuran (THF) in the presence of LiOH.H2O and dimethylsulfate (DMS). Quantitative methyl transfer from DMS preserves the atom economy.
- Basak, Anindita,Nayak, Mrinal K.,Chakraborti, Asit K.
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p. 4883 - 4886
(2007/10/03)
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- Molybdenum- and tungsten-catalyzed allylation of aromatic compounds with allylic esters and alcohols
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A novel method to substitute aromatic compounds with allylic groups using oxygen-containing allylic compounds in the presence of molybdenum or tungsten carbonyls under neutral conditions has been developed. The method is applicable to one step synthesis of methyl eugenol.
- Shimizu, Isao,Sakamoto, Toshiaki,Kawaragi, Saeko,Maruyama, Yooichiro,Yamamoto, Akio
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p. 137 - 138
(2007/10/03)
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- Substrate selective catalysis by rhodium metallohosts
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A novel supramolecular catalyst functioning according to the principles of enzymatic catalysis is described. It consists of a basket-shaped molecule to which a catalytically active Rh(I) complex is attached. The catalyst selectively hydrogenates and isomerizes allyl-substituted dihydroxyarene substrates that are bound in its cavity. The reactivity of this supramolecular catalyst and its affinity for several substrates is compared with that of the corresponding catalyst without a binding site. Features known from enzymatic catalysis, e.g. Michaelis-Menten kinetics and rate enhancement by cooperative binding, are described and discussed.
- Coolen, Hein K. A. C.,Meeuwis, Johannes A. M.,Van Leeuwen, Piet W. N. M.,Nolte, Roeland J. M.
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p. 11906 - 11913
(2007/10/03)
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- Monofluoro analogs of eugenol methyl ether as novel attractants for the oriental fruit fly
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Monofluoro analogs of eugenol methyl ether as potential attractants for the Oriental fruit fly (Bactrocera dorsalis, Hendel) were synthesized using selective fluorination reactions: electrophilic hydro- and iodofluorination, fluorodehydroxylation with (diethylamido)sulfur trifluoride (DAST), and Wittig fluoroolefination through the stabilized ylides. Unusual reduction of the double bond was detected in a reaction of eugenol methyl ether with pyridinium poly(hydrogen fluoride). Bis[(3,4-dimethoxyphenyl)alkyl] carbonates were identified as the novel nucleophilic substitution products of the intermediate generated from the reaction of 3,4-dimethoxybenzenealkanols with DAST. Reductive desulfonylation of fluorovinyl sulfone 24-(Z) with sodium amalgam afforded 1,2-dimethoxy-4-(3-fluoro-2-propenyl)benzene (E/Z = 85: 15) which was highly attractive to the Oriental fruit fly.
- Khrimian,DeMilo,Waters,Liquido,Nicholson
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p. 8034 - 8039
(2007/10/02)
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- Syntheses of (+/-)-Deoxyschizandrin and the Lignan, 1,4-Bis(3,4-dimethoxyphenyl)-2,3-dimethylbutane
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(+/-)-Deoxyschizandrin (1) has been synthesised through a dimerisation reaction as a key step.The Grignard reagent from 1-(3,4,5-trimethoxyphenyl)-2-bromopropane (10) on reaction with 2-t-butyl-3-phenyloxaziridine gives 1,4-bis(3,4,5-trimethoxyphenyl)-2,3-dimethylbutane (11), which is cyclised using vanadium oxytrifluoride to get deoxyschizandrin (1).Following the above methodology, 1,4-bis(3,4-dimethoxyphenyl)-2,3-dimethylbutane (2), a lignan has also been prepared.
- Gunasekaran, A.,Balasubramanian, K.
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p. 308 - 310
(2007/10/02)
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- REACTION OF o-BENZOQUINONE BISACETALS WITH ORGANOLITHIUMS. A NOVEL ROUTE TO SUBSTITUTED VERATROLES
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Substituted veratroles were easily obtained by the reaction of o-benzquinone bisacetals with organolithiums.
- Kikuchi, Yoshiyuki,Hasegawa, Yoko,Matsumoto, Masakatsu
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p. 2199 - 2202
(2007/10/02)
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