- GINGEROL DERIVATIVE HAVING INHIBITORY ACTIVITY AGAINST BIOFILM FORMATION AND PHARMACEUTICAL COMPOSITION COMPRISING SAME AS EFFECTIVE INGREDIENT FOR PREVENTING OR TREATING BIOFILM-CAUSED INFECTION SYMPTOM
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The present invention relates to a gingerol derivative having inhibitory activity against biofilm formation and a pharmaceutical composition for preventing or treating infections caused by biofilms including the gingerol derivative as an active ingredient. The gingerol derivative of the present invention exhibits significantly improved binding affinity for LasR and inhibitory activity against biofilm formation. Therefore, the gingerol derivative of the present invention can act on various membrane surfaces where biofilms tend to form and can effectively inhibit the formation of the corresponding biofilms. In addition, the use of the pharmaceutical composition according to the present invention can fundamentally prevent or treat a variety of infections caused by biofilms due to the presence of the gingerol derivative in the pharmaceutical composition.
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Paragraph 0032; 0051-0052; 0055-0056
(2020/09/22)
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- Discovery and Characterization of Pure RhlR Antagonists against Pseudomonas aeruginosa Infections
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Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic human pathogen that forms biofilms and produces virulence factors via quorum sensing (QS). Blocking the QS system in P. aeruginosa is an excellent strategy to reduce biofilm formation and the production of virulence factors. RhlR plays an essential role in the QS system of P. aeruginosa. We synthesized 55 analogues based on the chemical structure of 4-gingerol and evaluated their RhlR inhibitory activities using the cell-based reporter strain assay. Comprehensive structure-activity relationship studies identified the alkynyl ketone 30 as the most potent RhlR antagonist. This compound displayed selective RhlR antagonism over LasR and PqsR, strong inhibition of biofilm formation, and reduced production of virulence factors in P. aeruginosa. Furthermore, the survival rate of Tenebrio molitor larvae treated with 30 in vivo greatly improved. Therefore, compound 30, a pure RhlR antagonist, can be utilized for developing QS-modulating molecules in the control of P. aeruginosa infections.
- Nam, SangJin,Ham, So-Young,Kwon, Hongmok,Kim, Han-Shin,Moon, Suhyun,Lee, Jeong-Hoon,Lim, Taehyeong,Son, Sang-Hyun,Park, Hee-Deung,Byun, Youngjoo
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p. 8388 - 8407
(2020/09/21)
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- MnO2as a terminal oxidant in Wacker oxidation of homoallyl alcohols and terminal olefins
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Efficient and mild reaction conditions for Wacker-type oxidation of terminal olefins of less explored homoallyl alcohols to β-hydroxy-methyl ketones have been developed by using a Pd(ii) catalyst and MnO2 as a co-oxidant. The method involves mild reaction conditions and shows good functional group compatibility along with high regio- and chemoselectivity. While our earlier system of PdCl2/CrO3/HCl produced α,β-unsaturated ketones from homoallyl alcohols, the present method provided orthogonally the β-hydroxy-methyl ketones. No overoxidation or elimination of benzylic and/or β-hydroxy groups was observed. The method could be extended to the oxidation of simple terminal olefins as well, to methyl ketones, displaying its versatility. An application to the regioselective synthesis of gingerol is demonstrated.
- Fernandes, Rodney A.,Ramakrishna, Gujjula V.,Bethi, Venkati
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p. 6115 - 6125
(2020/10/27)
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- METHOD FOR PREPARING HIGHLY ENANTIO-ENRICHED GINGEROLS
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Disclosed is a method for preparing a chiral Gingerol compound. To prepare the chiral Gingerol compound, a racemic Gingerol compound is treated with kinetic resolution in the presence of a chiral catalyst compound and an alkali metal fluoride so a chiral Gingerol compound with high optical purity can be prepared. An oligo ethylene glycol-derived compound including an oligo ethylene glycol functional group, a basic part, and a hydroxy functional group of a binol derivative, an acidic part, can be used as a chiral catalyst compound.COPYRIGHT KIPO 2020
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Paragraph 0056-0061; 0133
(2019/12/25)
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- 6-gingerol derivative and its preparation and application
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A 6-gingerol derivative and its preparation and application are provided. That derivative has the following structure. The derivative of the present invention has antitumor activity and inhibit effect on tumor cells. In addition, the chemical properties o
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Paragraph 0093-0095; 0113-0116
(2019/10/07)
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- Kinetic Resolution of β-Hydroxy Carbonyl Compounds via Enantioselective Dehydration Using a Cation-Binding Catalyst: Facile Access to Enantiopure Chiral Aldols
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A practical and highly enantioselective nonenzymatic kinetic resolution of racemic β-hydroxy carbonyl (aldol) compounds through enantioselective dehydration process was developed using a cation-binding Song's oligoethylene glycol (oligoEG) catalyst with p
- Paladhi, Sushovan,Hwang, In-Soo,Yoo, Eun Jeong,Ryu, Do Hyun,Song, Choong Eui
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supporting information
p. 2003 - 2006
(2018/04/16)
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- Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents
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Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a master regulator of quorum sensing networks in P. aeruginosa. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section, stereochemistry and rotational rigidity in the middle section, and optimal alkyl chain length in the tail section are important factors for the enhancement of LasR-binding affinity and for the inhibition of biofilm formation. The most potent compound 41, an analog of (R)-8-gingerol with restricted rotation, showed stronger LasR-binding affinity and inhibition of biofilm formation than the known LasR antagonist (S)-6-gingerol. This new LasR antagonist can be used as an early lead compound for the development of anti-biofilm agents to treat P. aeruginosa infections.
- Choi, Hyunsuk,Ham, So-Young,Cha, Eunji,Shin, Yujin,Kim, Han-Shin,Bang, Jeong Kyu,Son, Sang-Hyun,Park, Hee-Deung,Byun, Youngjoo
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p. 9821 - 9837
(2017/12/26)
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- An Efficient Enantioselective Synthesis of Natural Gingerols, the Active Principles of Ginger
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A straightforward synthesis of (S)-gingerols 1-3 has been described. The requisite stereogenic center in the target molecules was introduced by Sharpless asymmetric dihydroxylation using a chiral complex, AD-mix β. This route is simple and efficient to prepare the products in very good yields.
- Ramesh Reddy,Wadavrao, Sachin B.,Yadav,Venkat Narsaiah
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p. 1009 - 1017
(2015/11/23)
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- Influence of side chain structure changes on antioxidant potency of the [6]-gingerol related compounds
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[6]-Gingerol and [6]-shogaol are the major pungent components in ginger with a variety of biological activities including antioxidant activity. To explore their structure determinants for antioxidant activity, we synthesized eight compounds differentiated by their side chains which are characteristic of the C1-C2 double bond, the C4-C5 double bond or the 5-OH, and the six- or twelve-carbon unbranched alkyl chain. Our results show that their antioxidant activity depends significantly on the side chain structure, the reaction mediums and substrates. Noticeably, existence of the 5-OH decreases their formal hydrogen-transfer and electron-donating abilities, but increases their DNA damage- and lipid peroxidation-protecting abilities. Additionally, despite significantly reducing their DNA strand breakage-inhibiting activity, extension of the chain length from six to twelve carbons enhances their anti-haemolysis activity.
- Lu, Dong-Liang,Li, Xiu-Zhuang,Dai, Fang,Kang, Yan-Fei,Li, Yan,Ma, Meng-Meng,Ren, Xiao-Rong,Du, Gao-Wei,Jin, Xiao-Ling,Zhou, Bo
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p. 191 - 197
(2014/06/24)
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- New scalable and eco-friendly synthesis of gingerols
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Synthesis of 6-gingerol and its congeners 7- and 9-gingerols has been achieved from eugenol by a new scalable and eco-friendly protocol. The key steps are functionalization of eugenol to the nitro compound and its reaction under optimized condition with terminal alkenes to afford intermediate isoxazolines. The latter on catalytic hydrogenation in presence of Raney nickel afford corresponding gingerols in good yields.
- Vijendra Kumar,Srinivas,Bettadaiah
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p. 2993 - 2995
(2012/07/31)
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- Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators
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In order to explore the structural determinants for the TRPV1 and TRPA1 agonist properties of gingerols, aseries of nineteen analogues (1b-5) of racemic [6]-gingerol (1a) was synthesized and tested on TRPV1 and TRPA1 channels. The exploration of the structure-activity relationships, by modulating the three pharmacophoric regions of [6]-gingerol, led to the identification of some selective TRPV1 agonists/desensitizers of TRPV1 channels (3a, 3f, and 4) and of some full TRPA1 antagonists (2c, 2d, 3b, and 3d). 2011 Elsevier Ltd. All rights reserved.
- Morera, Enrico,De Petrocellis, Luciano,Morera, Ludovica,Moriello, Aniello Schiano,Nalli, Marianna,Di Marzo, Vincenzo,Ortar, Giorgio
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p. 1674 - 1677
(2012/04/04)
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- Synthesis of gingerol and diarylheptanoids
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The synthesis of gingerol 1 and related compounds 2-5 along with diarylheptanoids 6-8 has been accomplished using a Keck allylation, Crimmins' aldol reaction, aldehyde coupling with acetylene, and chelation controlled reductions as the key reactions. The absolute configuration of these molecules was confirmed by preparing their acetonide derivatives and by comparison of the NMR data with natural compounds.
- Sabitha, Gowravaram,Srinivas, Chitti,Reddy, Teega Rammohan,Yadagiri, Kurra,Yadav, Jhillu Singh
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p. 2124 - 2133
(2012/03/27)
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- Synthesis of a new [6]-gingerol analogue and its protective effect with respect to the development of metabolic syndrome in mice fed a high-fat diet
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To determine the effects of a [6]-gingerol analogue (6G), a major chemical component of the ginger rhizome, and its stable analogue after digestion in simulated gastric fluid, aza-[6]-gingerol (A6G), on diet-induced body fat accumulation, we synthesized 6
- Okamoto, Mayumi,Irii, Hiroyuki,Tahara, Yu,Ishii, Hiroyuki,Hirao, Akiko,Udagawa, Haruhide,Hiramoto, Masaki,Yasuda, Kazuki,Takanishi, Atsuo,Shibata, Shigenobu,Shimizu, Isao
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experimental part
p. 6295 - 6304
(2011/11/07)
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- An enantioselective synthesis of (+)-(S)-[n]-gingerols via the l-proline-catalyzed aldol reaction
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An enantioselective approach to (+)-(S)-[n]-gingerols (1a-c) has been developed. The requisite stereogenic centers of target molecules are facilely constructed by the proline-catalyzed cross-aldol reaction from readily available achiral starting materials
- Ma, Shichao,Zhang, Shilei,Duan, Wenhu,Wang, Wei
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supporting information; experimental part
p. 3909 - 3911
(2010/03/25)
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- The stability of gingerol and shogaol in aqueous solutions
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Gingerols, pungent principles of ginger (the rhizome of Zingiber officinale), are biologically active components that may make a significant contribution towards medicinal applications of ginger and some products derived from ginger. Gingerols, however, are thermally labile due to the presence of a β-hydroxy keto group in the structure, and undergo dehydration readily to form the corresponding shogaols. This study investigated the stability of [6]-gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one] at temperatures ranging from 37 to 100°C in aqueous solutions, at pH 1, 4, and 7. Quantitative measurements of [6]-gingerol and its major degradation product [6]-shogaol [1-(4-hydroxy-3-methoxyphenyl)decan-4-ene-3-one] were performed by HPLC. Kinetics of [6]-gingerol degradation was characterized by least square fitting of a rate equation. It was found that gingerol exhibited novel reversible kinetics, in which it undergoes dehydration-hydration transformations with shogaol, the major degradation product. Degradation rates were found to be pH dependent with greatest stability observed at pH 4. The reversible degradation of [6]-gingerol at 100°C and pH 1 was relatively fast and reached equilibrium within 2 h. Activation energies for the forward and reverse reactions for [6]-gingerol were calculated from the Arrhenius equation using reaction rates obtained at temperatures ranging from 37 to 100°C.
- Bhattarai, Sushila,Van Tran, Hoan,Duke, Colin Charles
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p. 1658 - 1664
(2007/10/03)
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- A convenient one-step gingerol synthesis
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Racemic 6-gingerol can be obtained in a one-pot reaction by hexanal addition to the dianion of zingerone at low temperature. Similarly, addition of octanal or decanal to the dianion provides 8-gingerol or 10-gingerol, respectively. Acid treatment of the gingerols allows for formation of the corresponding shogaols.
- Fleming,Dyer,Eggington
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p. 1933 - 1939
(2007/10/03)
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- Short asymmetric synthesis of (+)(S) -gingerol from optically active β,δ-diketosulfoxide
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(+)(S) -Gingerol was synthesized in 3 steps via catecholborane reduction of the corresponding chiral β,δ-diketosulfoxide. (+)(S) -gingerol / β,δ-diketosulfoxides / (+)(R) 1-(p-tolylsulfinyl)-2-propan-2-one / catecholborane reduction
- Solladie, Guy,Ghiatou, Nasser
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p. 575 - 578
(2007/10/02)
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- An organo-iron mediated chiral synthesis of (+)-(S)-[6]-Gingerol
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A short and efficient synthesis of (+)-(S)-[6]-Gingerol is described. The key step is a highly stereoselective cycloaddition of a nitrile oxide with a chiral iron complexed triene.
- Le Gall,Lellouche,Beaucourt
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p. 6521 - 6524
(2007/10/02)
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- CHIRAL LEWIS ACIDS FOR ENANTIOSELECTIVE C-C BOND FORMATION
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The optically active Lewis acid 6 has been prepared and used in the enantioselective addition of enolsilanes and Me3SiCN to aldehydes.
- Reetz, M. T.,Kunisch, F.,Heitmann, P.
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p. 4721 - 4724
(2007/10/02)
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- C-C ASYMMETRIC BOND FORMATION MEDIATED BY OPTICALLY ACTIVE SULFOXIDES
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Highly stereoselective C-C bond forming reactions can be performed with a variety of optically active sulfinyl derivatives to afford, after desulfurization, optically active sulfur-free products.
- Cinquini, Mauro
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- NEW METHODS AND REAGENTS IN ORGANIC SYNTHESIS. 44. A NEW GENERAL EFFICIENT SYNTHESIS OF DL--GINGEROLS AND RELATIVES THROUGH DIRECT C-ACYLATION USING DIETHYL PHOSPHOROCYANIDATE (DEPC)
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DL--Gingerols (1) and their relatives, which have various interesting physiological actions, have been conveniently and efficiently prepared from ferulic acid (2) through direct C-acylation using diethyl phosphorocyanidate (DEPC) in the presence of triethylamine.KEYWORDS - -gingerol; C-acylation; diethyl phosphorocyanidate; β-ketonitrile; Grignard reaction; β-ketol
- Kato, Nobuharu,Hamada, Yasumasa,Shioiri, Takayuki
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p. 1679 - 1682
(2007/10/02)
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- Asymmetric Synthesis of a β-Ketol Moiety via 3,5-Disubstitute Isoxazoles: Application to (+)-(S)--Gingerol
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A new synthesis of (+/-)--gingerol (13), (+)-(S)--gingerol, and (+)-methyl--gingerol (12c) using 3,5-disubstituted isoxazoles as masked β-ketols, is described.Reductive fission of the labile N-O bond of the isoxazoles (8a) and (8b) gave the enami
- Giovanni, Baraldi Pier,Fabio, Moroder,Piero, Pollini Gian,Daniele, Simoni,Achille, Barco,Simonetta, Benetti
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p. 2983 - 2988
(2007/10/02)
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- Syntheses of the (+/-)--Gingerols (Pungent Principles of Ginger) and Related Compounds through Regioselective Aldol Condensations: Relative Pungency Assays
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The deprotonation of trimethylsilylzingerone (13) by lithium di-isopropylamide at -78 deg C has been found to be regioselective (92 : 8 in favour of less-substituted enolate): the anion was condensed with alkanals and acyl imidazoles to give convenient syntheses of (+/-)--- and --gingerols (1) and -, -, and -gingerdiones (9).Similary, 3-methoxy-4-trimethylsilyloxybenzylideneacetone (17) gave the (+/-)---dehydrogingerols (8) and -, -, and -dehydrogingerdiones (10).The aldol reaction to -gingerol and methyl -gingerol was also conducted through a vinyloxyborane or through the enol silyl ether (TiCl4 catalysis).Results of organoleptic assays on these compounds are discussed, and the relation between pungency in the gingerols and in capsaicin is commented on.The aldol method was also used to synthesise the natural β-ketols(+/-)-daphneolone (25) and (+/-)-hexahydrocurcumin (4).
- Dennif, Phillip,Macleod, Ian,Whiting, Donald A.
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- 3,5-Disubstituted Isoxazoles as a Latent Aldol Moiety: Application to the Synthesis of (+/-)--Gingerol
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(+/-)--Gingerol (9) has been synthesized by a route involving the use of a 3,5-disubstituted isoxazole derivative as an equivalent of the sensitive β-hydroxyketone unit.
- Barco, Achille,Benetti, Simonetta,Baraldi, Pier Giovanni,Guarneri, Mario,Pollini, Gian Piero,Simoni, Daniele
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p. 599 - 600
(2007/10/02)
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