- Synthesis of water soluble and multi-responsive selenopolypeptides via ring-opening polymerization of N-carboxyanhydrides
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We report here the synthesis of water soluble selenopolypeptides via the ring-opening polymerization of N-carboxyanhydrides. The oligoethylene glycol-bearing selenopolypeptides are thermally responsive in aqueous solutions with tunable lower critical solution temperatures. The polymers can also undergo rapid and reversible helix-coil transitions upon responding to the added redox cycle.
- Wu, Guangqi,Ge, Chenglong,Liu, Xingyi,Wang, Shuo,Wang, Letian,Yin, Lichen,Lu, Hua
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supporting information
p. 7860 - 7863
(2019/07/12)
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- An unprecedented medium-chain diunsaturated n-acylhomoserine lactone from marine roseobacter group bacteria
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N-acylhomoserine lactones (AHLs), bacterial signaling compounds involved in quorum-sensing, are a structurally diverse group of compounds. We describe here the identification, synthesis, occurrence and biological activity of a new AHL, N-((2E,5Z)-2,5-dodecadienoyl)homoserine lactone (11) and its isomer N-((3E,5Z)-3,5-dodecadienoyl)homoserine lactone (13), occurring in several Roseobacter group bacteria (Rhodobacteraceae). The analysis of 26 strains revealed the presence of 11 and 13 in six of them originating from the surface of the macroalgae Fucus spiralis or sediments from the North Sea. In addition, 18 other AHLs were detected in 12 strains. Compound identification was performed by GC/MS. Mass spectral analysis revealed a diunsaturated C12 homoserine lactone as structural element of the new AHL. Synthesis of three likely candidate compounds, 11, 13 and N-((2E,4E)-2,4-dodecadienoyl)homoserine lactone (5), revealed the former to be the natural AHLs. Bioactivity test with quorum-sensing reporter strains showed high activity of all three compounds. Therefore, the configuration and stereochemistry of the double bonds in the acyl chain seemed to be unimportant for the activity, although the chains have largely different shapes, solely the chain length determining activity. In combination with previous results with other Roseobacter group bacteria, we could show that there is wide variance between AHL composition within the strains. Furthermore, no association of certain AHLs with different habitats like macroalgal surfaces or sediment could be detected.
- Ziesche, Lisa,Wolter, Laura,Wang, Hui,Brinkhoff, Thorsten,Pohlner, Marion,Engelen, Bert,Wagner-D?bler, Irene,Schulz, Stefan
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- A cogeneration process for producing sulfur and sulfur on behalf of acetate acid diester method (by machine translation)
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The invention technical field of chemical synthesis, in particular relates to a methionine as raw material production process for producing sulfur and sulfur on behalf of acetate acid diester method. The invention states the payment proportional to production for preparing sulfur and sulfur on behalf of acetate acid diester method, in order to methionine and halogenated acetic acid as the raw material, the preparation comprising a homoserine lactone hydrohalide salt (IV), a sulfur acetate (I) and sulfur on behalf of the b b acid diester (II) of the three kinds of chemical products, and each between the products easy to separate and purify. (by machine translation)
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Paragraph 0081; 0083
(2018/12/02)
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- Small Molecule Inhibitors of the PCSK9·LDLR Interaction
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The protein-protein interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) is a relatively new, and extremely important, validated therapeutic target for treatment and prevention of heart disease. Experts in the area agree that the first small molecules to disrupt PCSK9·LDLR would represent a milestone in this field, yet few credible leads have been reported. This paper describes how side-chain orientations in preferred conformations of carefully designed chemotypes were compared with LDLR side chains at the PCSK9·LDLR interface to find molecules that would mimic interface regions of LDLR. This approach is an example of the procedure called EKO (Exploring Key Orientations). The guiding hypothesis on which EKO is based is that good matches indicate the chemotypes bearing the same side chains as the protein at the sites of overlay have the potential to disrupt the parent protein-protein interaction. In the event, the EKO procedure and one round of combinatorial fragment-based virtual docking led to the discovery of seven compounds that bound PCSK9 (SPR and ELISA) and had a favorable outcome in a cellular assay (hepatocyte uptake of fluorescently labeled low-density lipoprotein particles) and increased the expression LDLR on hepatocytes in culture. Three promising hit compounds in this series had dissociation constants for PCSK9 binding in the 20-40 μM range, and one of these was modified with a photoaffinity label and shown to form a covalent conjugate with PCSK9 on photolysis.
- Taechalertpaisarn, Jaru,Zhao, Bosheng,Liang, Xiaowen,Burgess, Kevin
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supporting information
p. 3242 - 3249
(2018/03/13)
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- Design, synthesis and activity evaluation study of novel substituted N-sulfonyl homoserine lactone derivatives as bacterial quorum sensing inhibitors
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A novel series of N-sulfonyl homoserine lactone derivatives 7a–7m has been designed, synthesized, and evaluated for quorum sensing inhibitory activities through the violacein inhibition in Chromobacterium violaceum CV026. Compound 7e displayed the high level of inhibitory activity among all the compounds synthesized. Studies of structure-activity relationship indicated that compounds with thiophene group in side chain showed better activity than those substituted by furan, pyrrole, pyridyl, and phenethyl group. Thiophene substituted compounds which connected electron withdrawing group exhibited better inhibitory activity relate to those connected electron donating group. Further analysis indicated that compound bearing an electron withdrawing substituent at the position 2 of their thiophene ring exhibited superior activity against violacein production to those bearing the substituent at the position 3 and 4. Compound 7e in particular, with IC50 value of 6.19 μM, were identified as promising lead compounds for further development.
- Sun, Qi,Zhao, Mingming,Liang, Jingwei,Xiao, Junhai,Meng, Fanhao
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p. 3345 - 3353
(2017/11/16)
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- N-SULFONYL HOMOSERINE LACTONE DERIVATIVES, PREPARATION METHOD THEREFOR AND USE
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The invention relates to a homoserine lactone derivative of Formula I, preparation method and use thereof. The compound has an effect of regulatory of bacterial quorum sensing, and is useful for preventing and/or treating a disease caused by infection of a bacterium.
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Paragraph 0066; 0067
(2017/04/11)
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- DERIVATIVE OF HOMOSERINE LACTONE, AND PREPARATION METHOD AND USE THEREOF
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Disclosed are a derivative of homoserine lactone represented by formula I, and a preparation method and use thereof. The compound has a bacterial quorum-sensing regulatory effect, and can be used for prevention and/or treatment of a disease caused by a bacterial infection.
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Paragraph 0040; 0041
(2015/12/31)
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- Haloperoxidase mediated quorum quenching by Nitzschia cf pellucida: Study of the metabolization of N-Acyl homoserine lactones by a benthic diatom
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Diatoms are known to produce a variety of halogenated compounds, which were recently shown to have a role in allelopathic interactions between competing species. The production of these compounds is linked to haloperoxidase activity. This research, has shown that this system may also be involved in diatom-bacteria interactions via the H2O2 dependent inactivation of a type of quorum sensing (QS) molecule, i.e., N-β-ketoacylated homoserine lactones (AHLs), by a natural haloperoxidase system from the benthic diatom Nitzschia cf pellucida. The AHL degradation pathway towards corresponding halogenated derivatives was elucidated via HPLC-MS analysis and the synthesis of a broad series of novel halogenated AHL analogues as reference compounds. Furthermore, their biological activity as quorum sensing modulators was directly compared and evaluated against a series of naturally occurring β-keto-AHLs. It has been demonstrated that the loss of the QS activity results from the final cleavage of the halogenated N-acyl chain of the signal molecules.
- Syrpas, Michail,Ruysbergh, Ewout,Blommaert, Lander,Vanelslander, Bart,Sabbe, Koen,Vyverman, Wim,De Kimpe, Norbert,Mangelinckx, Sven
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p. 352 - 367
(2014/02/14)
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- Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators
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Novel N-α-haloacylated homoserine lactones, in which a halogen atom was introduced at the α-position of the carbonyl function of the N - acyl chain, have been studied as quorum sensing (QS) modulators and compared with a library of natural N - acylated homoserine lactones (AHLs). The series of novel analogues consists of α-chloro, α-bromo and α-iodo AHL analogues. Furthermore, the biological QS activity of the synthetic AHL analogues compared to the natural AHLs was evaluated. Halogenated analogues demonstrated a reduced activity in the Escherichia coli JB523 bioassay, with the α-iodo lactones being the less active ones and the α-chloro AHLs the most potent QS agonists. Most of the α-haloacylated analogues did not exhibit a significant reduction when tested in the QS inhibition test. Therefore, these novel analogues could be utilized as chemical probes for QS structure-activity studies.
- Syrpas, Michail,Ruysbergh, Ewout,Stevens, Christian V.,De Kimpe, Norbert,Mangelinckx, Sven
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p. 2539 - 2549
(2015/02/19)
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- Synthesis and biological evaluation of triazole-containing N-acyl homoserine lactones as quorum sensing modulators
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Many bacterial species are capable of assessing their local population densities through a cell-cell signaling mechanism termed quorum sensing (QS). This intercellular communication process is mediated by small molecule or peptide ligands and their cognate protein receptors. Numerous pathogens use QS to initiate virulence once they achieve a threshold cell number on a host. Consequently, approaches to intercept QS have attracted considerable attention as potential anti-infective therapies. Our interest in the development of small molecule tools to modulate QS pathways motivated us to evaluate triazole-containing analogs of natural N-acyl l-homoserine lactone (AHL) signals as non-native QS agonists and antagonists in Gram-negative bacteria. We synthesized 72 triazole derivatives of five broad structure types in high yields and purities using efficient Cu(i)-catalyzed azide-alkyne couplings. These compounds were evaluated for their ability to activate or inhibit two QS receptors from two prevalent pathogens-LasR from Pseudomonas aeruginosa and AbaR from Acinetobacter baumannii-using bacterial reporter strains. Several triazole derivatives were identified that were capable of strongly modulating the activity of LasR and AbaR. These compounds represent a new and synthetically accessible class of AHL analogs, and could find utility as chemical tools to study QS and its role in bacterial virulence.
- Stacy, Danielle M.,Le Quement, Sebastian T.,Hansen, Casper L.,Clausen, Janie W.,Tolker-Nielsen, Tim,Brummond, Jacob W.,Givskov, Michael,Nielsen, Thomas E.,Blackwell, Helen E.
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supporting information
p. 938 - 954
(2013/02/26)
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- Design, synthesis and biological evaluation of N-sulfonyl homoserine lactone derivatives as inhibitors of quorum sensing in Chromobacterium violaceum
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A novel series of N-sulfonyl homoserine lactone derivatives 5a-l has been designed, synthesized and evaluated for quorum sensing inhibitory activities towards violacein production. Of the compounds synthesized, compound 5h was found to possess an excellent level of enantiopurity (99.2% e.e.). The results indicated that compounds bearing an ortho substituent on their phenyl ring exhibited excellent levels of inhibitory activity against violacein production. Compounds 5h and 5k in particular, with IC50 values of 1.64 and 1.66 μM, respectively, were identified as promising lead compounds for further structural modification.
- Zhao, Mingming,Yu, Yingying,Hua, Yuhui,Feng, Fan,Tong, Yigang,Yang, Xiaohong,Xiao, Junhai,Song, Hongrui
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p. 3266 - 3278
(2013/05/09)
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- METHODS AND INTERMEDIATES FOR PREPARING PHARMACEUTICAL AGENTS
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The invention provides methods and intermediates that are useful for preparing a compound of formula I: and salts thereof.
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Page/Page column 20
(2010/10/19)
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- A convenient synthesis of D,L-selenomethionine
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A convenient synthesis of D,L-selenomethionine from α-bromo-γ- butyrolactone in 4 steps and 26% overall yield has been described.
- Ran,Cao,Wang,Lin
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experimental part
p. 431 - 435
(2009/10/09)
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- Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic
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Parallel solution-phase synthesis of sulfide AHL analogues (10a-s) by one-pot or a sequential approach is reported. The corresponding sulfoxides 13a-e and sulfones 14a-e were prepared to expand the diversity of the 19-member array of sulfides 10a-s. Likewise, dithianes 12a-c were prepared with similarity both to sulfides 10a-s and to bioactive structures from garlic. Design and biological screening of all compounds presented in this work targeted inhibition of quorum-sensing comprising competitive inhibition of transcriptional regulators LuxR and LasR. The design was based on critical interactions within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-L-homoserine lactone (10c) was identified. Together with data collected for the other analogues, the resulting structure - activity relationship led to a hypothesis in which competitive binding was assumed.
- Persson, Tobias,Hansen, Thomas H.,Rasmussen, Thomas B.,Skinderso, Mette E.,Givskov, Michael,Nielsen, John
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p. 253 - 262
(2007/10/03)
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- Method for synthesizing oxazinones
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New methods and intermediates are discussed for the stereospecific synthesis of oxazinone compounds.
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- Cyclic hydroxamates, especially multiply substituted [1,2]oxazinan-3-ones
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Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride - alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one.
- Wolfe, Saul,Wilson, Marie-Claire,Cheng, Ming-Huei,Shustov, Gennady V.,Akuche, Christiana I.
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p. 937 - 960
(2007/10/03)
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- COMPOUNDS AND METHODS FOR CONTROLLING BACTERIAL VIRULENCE
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Novel sulfonated homoserine lactones formula I have been found to act ac quorum sensing inhibitors. As such, they may be useful in the treatment of bacterial infections.
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- Studies toward the synthesis of (+)-palustrine: The first asymmetric synthesis of (-)-methyl palustramate
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The stereoselective synthesis of (-)-methyl palustramate, a possible intermediate for the synthesis of (+)-palustrine, is described. The key step of the synthesis is a conformationally restricted Claisen rearrangement to afford the highly functionalized 1-benzylpipecolic ester 10. In addition, a new procedure for debenzylation of 1-benzylpiperidines (Li, NH2CH2)2, Et3N, THF) was used to remove the benzyl protecting group where traditional methods failed.
- Angle, Steven R.,Henry, Robert M.
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p. 7490 - 7497
(2007/10/03)
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