937-32-6Relevant articles and documents
Tryptophan trimers and tetramers inhibit dengue and Zika virus replication by interfering with viral attachment processes
Fikatas, Antonios,Meyen, Eef,Noppen, Sam,Pannecouque, Christophe,Schols, Dominique,Vervaeke, Peter,Camarasa, María-José,Martí-Marí, Olaia,Martínez-Guald, Belén,San-Félix, Ana
supporting information, (2020/02/29)
Here, we report a class of tryptophan trimers and tetramers that inhibit (at low micromolar range) dengue and Zika virus infection in vitro. These compounds (AL family) have three or four peripheral tryptophan moieties directly linked to a central scaffold through their amino groups; thus, their carboxylic acid groups are free and exposed to the periphery. Structure-activity relationship (SAR) studies demonstrated that the presence of extra phenyl rings with substituents other than COOH at the N1 or C2 position of the indole side chain is a requisite for the antiviral activity against both viruses. The molecules showed potent antiviral activity, with low cytotoxicity, when evaluated on different cell lines. Moreover, they were active against laboratory and clinical strains of all four serotypes of dengue virus as well as a selected group of Zika virus strains. Additional mechanistic studies performed with the two most potent compounds (AL439 and AL440) demonstrated an interaction with the viral envelope glycoprotein (domain III) of dengue 2 virus, preventing virus attachment to the host cell membrane. Since no antiviral agent is approved at the moment against these two flaviviruses, further pharmacokinetic studies with these molecules are needed for their development as future therapeutic/prophylactic drugs.
Synthesis of 4-chalcogenyl pyrazoles via electrophilic chalcogenation/cyclization of α,β-alkynic hydrazones
Cheng, Yu-Fei,Gao, Wen-Chao,Niu, Yulan,Shang, Yu-Zhu,Tian, Jun,Yu, Xinzhang
, p. 1806 - 1811 (2020/03/17)
A facile method for the synthesis of 4-chalcogenylated pyrazoles has been developed via electrophilic chalcogenation/cyclization of α,β-alkynic hydrazones. The cyclization of α,β-alkynic aldehyde hydrazones could be induced by using either sulfenyl chloride or the S-electrophiles generated in situ from the reaction of NCS and arythiol. The developed method was successfully applied to the synthesis of the sulfenyl analogue of celecoxib.
Increasing Scope of Clickable Fluorophores: Electrophilic Substitution of Ylidenemalononitriles
De Souza, Juliana M.,Abdiaj, Irini,Chen, Jiaqi,Hanson, Kenneth,De Oliveira, Kleber T.,McQuade, D. Tyler
, p. 11822 - 11834 (2020/10/23)
Recently, we demonstrated that ylidenemalononitriles (YMs) react with amines to form cyclic amidines and that the starting linear YMs are nonemissive in solution and the cyclic amidines are fluorescent. These turn-on systems were of interest to us because of their potential as biosensors and synthons for accessing functionalized pyridines. While our original method was promising, several limitations persisted, including access to more functionalized and polar-solvent-soluble structures as well as increased control over the rate of cyclization. Herein, we report a new approach that allows the electrophilic substitution of YMs. These substituted YMs exhibit faster turn-on rates, color tunability, access to polar-solvent-soluble species, and increased control over cyclization rate. This allowed us to significantly expand the fluorophore's chemical space.
In Situ Activation of Disulfides for Multicomponent Reactions with Isocyanides and a Broad Range of Nucleophiles
Lei, Xiaofang,Wang, Yuanyuan,Fan, Erkang,Sun, Zhihua
supporting information, p. 1484 - 1487 (2019/02/26)
Activation of disulfides with N-halogen succinimide in the presence of TEMPO allows insertion reaction by an isocyanide, the product of which can further accept a wide range of nucleophiles for the generation of isothioureas and related molecular moieties. This new procedure overcomes previous methods that accept essentially only aryl amines as the third nucleophilic component. The diverse nucleophiles usable in our new protocol make this approach a general method for de novo synthesis of many S-containing heterocycles.
Reactivity of the nitrogen-centered tryptophanyl radical in the catalysis by the radical SAM enzyme NosL
Qianzhu, Haocheng,Ji, Wenjuan,Ji, Xinjian,Chu, Leixia,Guo, Chuchu,Lu, Wei,Ding, Wei,Gao, Jiangtao,Zhang, Qi
supporting information, p. 344 - 347 (2017/01/03)
The radical SAM tryptophan (Trp) lyase NosL involved in nosiheptide biosynthesis catalyzes two parallel reactions, converting l-Trp to 3-methyl-2-indolic acid (MIA) and to dehydroglycine and 3-methylindole, respectively. The two parallel reactions diverge from a nitrogen-centered tryptophanyl radical intermediate. Here we report an investigation on the intrinsic reactivity of the tryptophanyl radical using a chemical model study and DFT calculations. The kinetics of the formation and fragmentation of this nitrogen-centered radical in NosL catalysis were also studied in detail. Our analysis explains the intriguing catalytic promiscuity of NosL and highlights the remarkable role this enzyme plays in achieving an energetically highly unfavorable transformation.
Diaryl and heteroaryl sulfides: Synthesis via sulfenyl chlorides and evaluation as selective anti-breast-cancer agents
Yonova, Ivelina M.,Osborne, Charlotte A.,Morrissette, Naomi S.,Jarvo, Elizabeth R.
, p. 1947 - 1953 (2014/04/03)
A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described. In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted with arylzinc reagents. This method tolerates functional groups including aryl fluorides and chlorides, ketones, as well as N-heterocycles including pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized by this method exhibited selective activity against the MCF-7 breast cancer cell line in the micromolar range.
Synthesis and evaluation of novel sulfenamides as novel anti Methicillin-resistant Staphylococcus aureus agents
Shang, Jian-Li,Guo, Hui,Li, Zai-Shun,Ren, Biao,Li, Zheng-Ming,Dai, Huan-Qin,Zhang, Li-Xin,Wang, Jian-Guo
supporting information, p. 724 - 727 (2013/02/25)
A total of 29 novel sulfenamide compounds were synthesized, spectroscopically characterized and evaluated in vitro for antimicrobial activity against various infectious pathogens. Compounds 1b and 2c exhibited potent inhibition against clinical Methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) values of 1.56 μg/mL.
[4+2] Cyclohexane ring formation by a tandem of a free radical alkylation of a non-activated δ-carbon atom and intramolecular carbanion cycloalkylation
Petrovic, Goran,Cekovic, Zivorad
, p. 1671 - 1679 (2007/10/03)
A [4+2] cyclohexane ring formation was achieved by the combination of free radical and ionic reaction sequences. Free radical alkylation of the remote non-activated δ-carbon atom involves addition of δ-carbon radicals, generated by 1,5-hydrogen transfer in alkoxyl radical intermediates, to the radicophilic olefins, while the polar sequence involves the enolate anions as intermediates which undergo a cycloalkylation reaction. The cyclohexane rings were constructed using diverse acyclic compounds 15 and 18 as well as cyclic alkyl arenesulfenates (e.g., 5, 24, 27) as the precursors of alkoxyl radicals (four-carbon atom fragment) and methyl vinyl ketone or other activated olefins as two-carbon atom fragments. Annulation of the cyclohexane ring was applied for the synthesis of a variety of cyclic systems including monocyclic (17 and 20), fused-rings (e.g. 23, 26, 29) and spirocyclic systems (7).
Substituent effect on the competition between hetero-Diels-Alder and cheletropic additions of sulfur dioxide to 1-substituted buta-1,3-dienes
Roversi, Elena,Monnat, Frederic,Vogel, Pierre,Schenk, Kurt,Roversi, Pietro
, p. 733 - 760 (2007/10/03)
The reactivity of sulfur dioxide toward variously substituted butadienes was explored in an effort to define the factors affecting the competition between the hetero-Diels-Alder and cheletropic additions. At low temperature (2 in the hetero-Diels-Alder mode in the presence of CF3COOH as promoter. In the case of (E)-1-ethylidene-2-methylidenecyclohexane ((E)-4a), the [4+2] cycloaddition of SO2 is fast at -90° without acid catalyst. (E)-1-(Acyloxy)buta-1,3-dienes (E)-1c, (E)-1y, and (E)-1z with AcO, BzO, and naphthalene-2-(carbonyloxy). substituents, respectively also undergo the hetero-Diels-Alder addition with SO2+CF3COOH at low temperatures, giving a 1:10 mixture of the corresponding cis- and trans-6-(acyloxy)sultines c-2c,y,z and t-2c,y,z, respectively). Above -50°, the sultines undergo complete cycloreversion to the corresponding dienes and SO2, which that add in the cheletropic mode at higher temperature to give the corresponding 2-substituted sulfolenes (=2,5-dihydrothiophene 1,1-dioxides) 3. The hetero-Diels-Alder additions of SO2 follow the Alder endo rule, giving first the 6-substituted cis-sultines that equilibrate then with the more stable trans-isomers. This statement is based on the assumption that the S=O group in the sultine prefers a pseudo-axial rather than a pseudo-equatorial position, as predicted by quantum calculations. The most striking observation is that electron-rich dienes such as 1-cyclopropyl-, 1-phenyl-, 1-(4-methoxyphenyl)-, 1-(trimethylsilyl)-, 1-phenoxy-, 1-(4-chlorophenoxy)-, 1-(4-methoxyphenoxy)-, 1-(4-nitrophenoxy)-, 1-(naphthalen-2-yloxy)-, 1-(methylthio)-, 1-(phenylthio)-, 1-[(4-chlorophenyl)thio]-, 1-[(4-methoxyphenyl)thio]-, 1-[(4-nitrophenyl)thio]-, and 1-(phenylseleno)buta-1,3-diene, as well as 1-(methoxymethylidene)-2-methylidenecyclohexane (4f) do not equilibrate with the corresponding sultines between -100 and -10°, in the presence of a large excess of SO2, with or without acidic promoter. The hetero-Diels-Alder additions of SO2 to 1-substituted (E)-buta-1,3-dienes are highly regioselective, giving exclusively the corresponding 6-substituted sultines. The 1-substituted (Z)-buta-1,3-dienes do not undergo the hetero-Diels-Alder additions with sulfur dioxide.
Pyridyl-substituted thioaminyl stable free radicals: Isolation, ESR spectra, and magnetic characterization
Miura, Yozo,Kurokawa, Shinya,Nakatsuji, Masaaki,Ando, Kenjiro,Teki, Yoshio
, p. 8295 - 8303 (2007/10/03)
N-[(4-Nitrophenyl)thio]- (1a) and N-[(2,4-dichlorophenyl)thio)]-2,6- diphenyl-4-(3-pyridyl)phenylaminyl (1b), N-[(4-nitrophenyl)thio]- (2a) and N- [(2,4-dichlorophenyl)thio]-4-phenyl-2,6-di(3-pyridyl)-phenylaminyl (2b), and N-[(2,4-dichlorophenyl)thio]-2,6-diphenyl(4-pyridyl)aminyl (3) were generated by PbO2 oxidation of the corresponding precursors. Although 3 was not sufficiently stable to be isolated, both 1 and 2 persisted in solution without decomposition and could be isolated as radical crystals. X-ray crystallographic analysis of 1b revealed that the Ar-N-S-Ar' π-framework is approximately planar and the 2- and 6-phenyl groups are significantly twisted from this plane. The magnetic susceptibility measurements for the isolated radical crystals were carried out using a SQUID magnetometer in the temperature range 1.8-300 K. The susceptibilities of 1a and 2a were explained in terms of a one-dimensional (1D) antiferromagnetic (AFM) regular Heisenberg model with an exchange interaction of 2J/k(B) = -63.4 and -17.8 K, respectively, and that of 1b was interpreted in terms of a 1D AFM alternating Heisenberg model with 2J/k(B) = -12.8 K and α (alternation parameter) = 0.91. On the other hand, that of 2b was explained in terms of a 1D ferromagnetic regular Heisenberg model with 2J/k(B) = 22.4 K.
