- Synthesis and analysis of stable isotope-labelled: N -acyl homoserine lactones
-
Aliphatic aldehydes were deuterated at the α-position via a base-catalyzed exchange reaction with D2O. These deuterated building blocks were used for the synthesis of labelled analogues of quorum sensing signal molecules belonging to the three major classes of naturally occurring N-acylated homoserine lactones (AHLs), with the label on a non-enolizable and therefore stable position. Besides the application of these stable isotope-labelled AHLs as a labelled standard for analysis via isotope dilution mass spectrometry, these compounds can be used to study the metabolic fate of the fatty acid tail of the AHL-molecule. These isotope-labelled compounds were fully characterized and used to synthesize the deuterated analogues of two commonly occurring AHL-degradation products, a tetramic acid and a ring opened N-acyl homoserine.
- Ruysbergh, Ewout,Stevens, Christian V.,De Kimpe, Norbert,Mangelinckx, Sven
-
-
Read Online
- Reductase of Mutanobactin Synthetase Triggers Sequential C-C Macrocyclization, C-S Bond Formation, and C-C Bond Cleavage
-
Mutanobactins (MUBs) and their congeners that contain a macrocycle and/or a thiazepane ring are lipopeptides from Streptococcus mutans, a major causative agent of dental caries. Here we show that the C-terminal reductase domain of MubD releases the lipohexapeptide intermediates in an aldehyde form, which enables a spontaneous C-C macrocyclization. In the presence of a thiol group, the macrocyclized MUBs can further undergo spontaneous C-S bond formation and C-C bond cleavage to generate diverse MUB congeners.
- Wang, Min,Xie, Zhoujie,Tang, Shoubin,Chang, Ee Ling,Tang, Yue,Guo, Zhengyan,Cui, Yinglu,Wu, Bian,Ye, Tao,Chen, Yihua
-
-
Read Online
- Synthesis and antimicrobial activity of novel 4-Hydroxy-2-quinolone analogs
-
Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug discovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long alkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized. The antibacterial and antifungal activities of these analogs against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were investigated. The structure-activity relationship study revealed that the length of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial activities. Particularly, the brominated analogs 3j with a nonyl side chain exhibited exceptional antifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 μg/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity against S. aureus, although not as potent, showed a similar trend to the antifungal activity. The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment.
- Khamkhenshorngphanuch, Thitiphong,Kulkraisri, Kittipat,Janjamratsaeng, Alongkorn,Plabutong, Napasawan,Thammahong, Arsa,Manadee, Kanitta,Na Pombejra, Sarisa,Khotavivattana, Tanatorn
-
-
- COMPOUNDS HAVING AGONISTIC EFFECT AGAINST GPR84, PREPARATION METHOD FOR COMPOUNDS AND USE OF COMPOUNDS
-
The present invention relates to a class of compounds represented by the formula I, or pharmaceutically acceptable salts thereof, methods for their preparation, and application as small molecule tools that function as GPR84 agonists, and their use in preparing a medicament for the treatment of septicemia.
- -
-
Paragraph 0130; 0131
(2018/09/12)
-
- Succinct synthesis of saturated hydroxy fatty acids and: In vitro evaluation of all hydroxylauric acids on FFA1, FFA4 and GPR84
-
Saturated hydroxy fatty acids make up a class of underexplored lipids with potentially interesting biological activities. We report a succinct and general synthetic route to saturated hydroxy fatty acids hydroxylated at position 6 or higher, and exemplify this with the synthesis of hydroxylauric acids. All regioisomers of hydroxylauric acids were tested on free fatty acid receptors FFA1, FFA4 and GPR84. The results show that the introduction of a hydroxy group and its position have a high impact on receptor activity.
- Kaspersen, Mads Holmgaard,Jenkins, Laura,Dunlop, Julia,Milligan, Graeme,Ulven, Trond
-
supporting information
p. 1360 - 1365
(2017/07/07)
-
- Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists
-
A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.
- Liu, Yang,Zhang, Qing,Chen, Lin-Hai,Yang, Hui,Lu, Wei,Xie, Xin,Nan, Fa-Jun
-
supporting information
p. 579 - 583
(2016/07/06)
-
- A Continuous, Fluorogenic Sirtuin 2 Deacylase Assay: Substrate Screening and Inhibitor Evaluation
-
Sirtuins are important regulators of lysine acylation, which is implicated in cellular metabolism and transcriptional control. This makes the sirtuin class of enzymes interesting targets for development of small molecule probes with pharmaceutical potential. To achieve detailed profiling and kinetic insight regarding sirtuin inhibitors, it is important to have access to efficient assays. In this work, we report readily synthesized fluorogenic substrates enabling enzyme-economical evaluation of SIRT2 inhibitors in a continuous assay format as well as evaluation of the properties of SIRT2 as a long chain deacylase enzyme. Novel enzymatic activities of SIRT2 were thus established in vitro, which warrant further investigation, and two known inhibitors, suramin and SirReal2, were profiled against substrates containing ε-N-acyllysine modifications of varying length.
- Galleano, Iacopo,Schiedel, Matthias,Jung, Manfred,Madsen, Andreas S.,Olsen, Christian A.
-
supporting information
p. 1021 - 1031
(2016/02/23)
-
- Continuous flow synthesis of toxic ethyl diazoacetate for utilization in an integrated microfluidic system
-
An integrated microfluidic system for multiple reactions and separations of hazardous ethyl diazoacetate is presented. The integrated techniques include: a droplet technique for liquid-liquid and/or gas-liquid separation and in situ generation of the toxic reagent, a dual channel membrane technique based on a cheap polymeric microseparator for liquid-liquid separation, and a capillary microreactor for carrying out cascade reactions in a sequential and continuous manner.
- Maurya, Ram Awatar,Min, Kyoung-Ik,Kim, Dong-Pyo
-
supporting information
p. 116 - 120
(2014/01/06)
-
- AMIDE COMPOUND AND BACTERIAL DISEASE CONTROL AGENT FOR AGRICULTURAL AND HORTICULTURAL USE
-
The present invention provides an amide compound having antibacterial activity, and a bacterial infection control agent for agricultural and horticultural use that contains the amide compound. The novel amide compound of the present invention is represented by General Formula (1): wherein R is a -CH(R1)(R2) or a -CO(R2) group, R1 is a hydrogen atom or a hydroxyl group, and R2 is a C1-12 alkyl group.
- -
-
Page/Page column 11-12
(2010/09/05)
-
- AMIDE COMPOUND, SALT THEREOF, AND BIOFILM REMOVER USING THEM
-
The present invention provides a biofilm stripping agent for removing biofilms already formed. The biofilm stripping agent of the present invention contains, as an active ingredient, an amide compound or salt thereof denoted by General Formula (1), wherein R is a C1-11 alkyl group, and Q is a substituent denoted by the following Formulas (Q1), (Q2) or (Q3), wherein, in Formula (Q1), n is an integer ranging from 0 to 4; in Formula (Q2), R1 is a C1-4 alkyl group, and R2 is a hydroxyl group or carbamoyl group; in Formula (Q3), R3 is a hydrogen atom, hydroxyl group or carbamoyl group.
- -
-
-
- Synthesis of novel &β-lactone inhibitors of fatty acid synthase
-
Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a β-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the α- and β-alkyl chains, their chemical composition, and amino ester substitutions were altered and the resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display an increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.
- Richardson, Robyn D.,Knowles, Lynn M.,Cieplak, Piotr,Smith, Jeffrey W.,Ma, Gil,Oyola, Yatsandra,Zancanella, Manuel,Romo, Daniel
-
scheme or table
p. 5285 - 5296
(2010/04/02)
-
- Substitution of acyl for acetyl with N-acylbenzotriazoles catalyzed by samarium triiodide
-
Catalyzed by samarium triiodide (SmI3), substitution of acyl with N-acylbenzotriazoles for acetyl in acetoacetic esters and acetylacetone proceeds smoothly under neutral conditions in open air, affording the corresponding β-keto esters and β-diketones in good yields. Copyright Taylor & Francis Group, LLC.
- Zou, Xuefei,Jia, Xiaofei,Wang, Xiaoxia,Xie, Guanqun
-
p. 1617 - 1625
(2008/02/01)
-
- Discrimination of β-ketoesters by ruthenium(II)-binap-catalyzed asymmetric hydrogenation
-
(Chemical Equation Presented) Please, after you... β-Ketoesters in mixtures underwent Noyori reduction one by one at room temperature under 4 bar of hydrogen pressure in the presence of a catalyst formed from RuII and (S)-binap (see example). The rate of the asymmetric hydrogenation and hence the selectivity for a particular β-ketoester was found to depend on the Lewis basicity of the ester group. Binap = 2,2′-bis(diphenylphosphanyl)-1, 1′-binaphthyl.
- Kramer, Rainer,Brueckner, Reinhard
-
p. 6537 - 6541
(2008/09/17)
-
- Synthesis of 4-alkyl- and 4-(ω-chloroalkyl)-3-hydroxy-5- alkylidenebutenolides based on cyclizations of 4-alkyl- and 4-(ω- chloroalkyl)-1,3-bis(trimethylsilyloxy)buta-1,3-dienes with oxalyl chloride
-
4-Alkyl- and 4-(ω-chloroalkyl)-1,3-bis(trimethylsilyloxy)buta-1,3- dienes were prepared from ethyl acetoacetate in three steps. Their cyclization with oxalyl chloride allowed an efficient synthesis of 4-alkyl- and 4-(ω-chloroalkyl)-5-alkylidenebutenolides. Georg Thieme Verlag Stuttgart.
- Nguyen, Van Thi Hong,Bellur, Esen,Appel, Bettina,Langer, Peter
-
p. 2865 - 2872
(2008/02/07)
-
- An efficient synthesis of novel N-acetyl-3-alkanoyl and 3-dienoyl tetramic acids
-
A general synthesis of N-acetyl-3-alkanoyl- and 3-dienoyl-tetramic acids is presented. The condensation of N-(N-acetylglycyloxy)succinimide with β-keto esters bearing alkanoyl or dienoyl groups furnishes the new 3-substituted N-acetyltetramic acids 6-9 and 16 in good yields. The key intermediates 4 and 5 have been isolated and subsequently cyclized to the corresponding tetramic acids. Spectral data for and the physical characteristics of all compounds are reported.
- Petroliagi, Margarita,Igglessi-Markopoulou, Olga
-
p. 3543 - 3548
(2007/10/03)
-
- A novel convenient route to the naturally occurring 3-oxoacyl-L-homoserinelactones and related bacterial autoinducers
-
The naturally occurring 3-oxohexanoyl-L-homoserinelactone (1a), a bacterial autoinducer has been prepared in 47% overall yield by condensing stable 3-oxohexanoic acid (2), prepared by hydrolysis from the corresponding ester (3), with L-homoserinelactone using hydroxybenzotriazole (HOBT) and dicyclohexylcarbodiimide (DCC) in non-aqueous media.
- Dekhane, Mouloud,Douglas, Kenneth T.,Gilbert, Peter
-
p. 1883 - 1884
(2007/10/03)
-
- Inhibitors of acyl-CoA:cholesterol acyltransferase. 5. Identification and structure-activity relationships of novel β-ketoamides as hypocholesterolemic agents
-
A study of structure-activity relationships of substituted β-ketoamide ACAT inhibitors I and II was performed. The results of this study suggest that whereas the β-keto group was tolerated with no loss in activity, β- hydroxy and oxime moieties led to significantly reduced activity in vitro and in vivo. The most potent inhibitor from the acyclic series (I) (11, IC50 = 0.006 μM) contained a C-13 alkyl chain. This compound reduced plasma total cholesterol by 38% and 66% at 3 and 30 mg/kg, respectively, in cholesterol- fed rats. Dimethylation α to the anilide core (5) and subsequent N- methylation of the amide NH (6) decreased in vitro potency significantly. It was also found that high potency was retained with inhibitors which incorporated the carbonyl into a lactam ring (II).
- Augelli-Szafran,Blankley,Roth,Trivedi,Bousley,Essenburg,Hamelehle,Krause,Stanfield
-
p. 2943 - 2949
(2007/10/02)
-
- Preparation of γ-Substituted β-Oxoesters with a New Heterocyclic Synthon
-
Ethyl 2,5-dihydro-2,3-dimethyl-5-oxoisoxazole-4-carboxylate was alkylated and acylated via its potassium-salt generated by potassium t-butoxide under convenient conditions.Hydrolysis of the enamines obtained by the catalytic hydrogenation of the 3-alkylated/acetylated derivatives affords β-oxo and β,δ-dioxoesters, respectively.Hydrogenolysis of the 3-acyl derivatives allows the regiospecific synthesis of β-enamino-δ-oxoesters.
- Doleschall, Gabor,Seres, Peter,Kovacs, Attila
-
p. 324 - 346
(2007/10/02)
-
- A NEW ENAMINE-SALT FOR THE SYNTHESIS OF γ-ALKYLATED ETHYL ACETOACETATE DERIVATIVES
-
A convenient method for the preparation of γ-alkylated ethyl acetoacetate from alkyl halides via a new isoxazole enamine-salts is reported.
- Doleschall, G.
-
p. 6339 - 6340
(2007/10/02)
-