Generic placeholder image

Mini-Reviews in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

Review Article

Pyroglutamic Acid and its Derivatives: The Privileged Precursors for the Asymmetric Synthesis of Bioactive Natural Products

Author(s): Sharad Kumar Panday*

Volume 17, Issue 6, 2020

Page: [626 - 646] Pages: 21

DOI: 10.2174/1570193X16666190917142814

Price: $65

Abstract

Pyroglutamic acid is one of the privileged asymmetric precursors for the synthesis of a variety of molecules such as Angiotensin-Converting Enzyme (ACE) inhibitors, angiotensin II receptor subtypes (AT-1 receptor antagonists), as well as bioactive natural products. Starting with primary reports in 1980’s, last almost four decades has witnessed a rapid overgrowth of publications using pyroglutamic acid as a preferred asymmetric precursor and these have been well documented. Pyroglutamic acid has two differential carbonyl groups a lactam carbonyl and a carboxylic functionality along with an NH group, and all of these functionalities can be further derivatized/ transformed and in turn opened avenues for the synthesis of variety of molecules. Derived easily from glutamic acid by internal cyclization, pyroglutamic acid offers a cheap and very good source of chirality and has provided an important tool for the synthesis of natural products/intermediates to natural products. Herein, we wish to describe the exploitation of the chemistry of pyroglutamic acid and its derivatives in the asymmetric synthesis of natural products establishing its versatility as a privileged asymmetric precursor.

Keywords: Asymmetric synthesis, bioactive molecules, natural products, privileged asymmetric precursor, pyroglutamic acid derivatives, pyroglutamic acid.

Graphical Abstract

[1]
Song, Y.; Chen, W.; Kang, D.; Zhang, Q.; Zhan, P.; Liu, X. Old friends in new guise: Exploiting privileged structures for scaffold re-evolution/refining. Comb. Chem. High Throughput Screen., 2014, 17(6), 536-553.
[http://dx.doi.org/10.2174/1386207317666140122101631] [PMID: 24446784]
[2]
Song, Y.; Zhan, P.; Liu, X. Heterocycle-thioacetic acid motif: A privileged molecular scaffold with potent, broad-ranging pharmacological activities. Curr. Pharm. Des., 2013, 19(40), 7141-7154.
[http://dx.doi.org/10.2174/13816128113199990505] [PMID: 23859548]
[3]
Song, Y.; Zhan, P.; Zhang, Q.; Liu, X. Privileged scaffolds or promiscuous binders: A glance of pyrrolo[2,1-f][1,2,4]triazines and related bridgehead nitrogen heterocycles in medicinal chemistry. Curr. Pharm. Des., 2013, 19(8), 1528-1548.
[PMID: 23131184]
[4]
Ohfune, Y.; Tomita, M. Total synthesis of (-)-domoic acid. A revision of the original structure. J. Am. Chem. Soc., 1982, 104, 3511-3513.
[http://dx.doi.org/10.1021/ja00376a048]
[5]
Thottahil, J.K.; Moniot, J.L.; Mueller, R.H.; Wong, M.K.Y.; Kissick, T.P. Conversion of L-pyroglutamic acid to 4-alkylsubstituted L-prolines, The synthesis of trans-4-cyclohexyl-Lproline. J. Org. Chem., 1986, 51, 3140-3143.
[http://dx.doi.org/10.1021/jo00366a011]
[6]
Thottahil, J.K.; Moniot, J.L. Lithium diphenylcuprate reac-tions with 4-tosyloxy-L-prolines; an interesting stereochemical outcome: A synthesis of Trans-4-phenyl-L-proline. Tetrahedron Lett., 1986, 27, 151-154.
[http://dx.doi.org/10.1016/S0040-4039(00)83964-7]
[7]
Imaki, K.; Sakuyama, S.; Okada, T.; Toda, M.; Hayashi, M.; Miyamoto, T.; Kawasaki, A.; Okegawa, T. Potent orally active inhibitors of Angiotensin-Converting Enzyme (ACE). Chem. Pharm. Bull. (Tokyo), 1981, 29(8), 2210-2214.
[http://dx.doi.org/10.1248/cpb.29.2210] [PMID: 6274523]
[8]
Panday, S.K.; Dikshit, D.K.; Dikshit, M. Synthesis of N-[3′-(acetylthio)alkanoyl] and N-[3′-mercaptoalkanoyl]-4-a(s)-(phenylmethyl) pyroglutamic acids and prolines as potent ACE inhibitors. Med. Chem. Res., 2009, 18, 566-578.
[http://dx.doi.org/10.1007/s00044-008-9150-z]
[9]
Mavromoustakos, T.; Moutevelis-Minakakis, P.; Kokotos, C.G.; Kontogianni, P.; Politi, A.; Zoumpoulakis, P.; Findlay, J.; Cox, A.; Balmforth, A.; Zoga, A.; Iliodromitis, E. Synthesis, binding studies and in vivo biological evaluation of novel non-peptide antihypertensive analogues. Bioorg. Med. Chem., 2006, 14(13), 4353-4360.
[http://dx.doi.org/10.1016/j.bmc.2006.02.044] [PMID: 16546395]
[10]
Prasad, J.; Pathak, M.B.; Panday, S.K. An efficient and straight forward synthesis of (5S)-1-benzyl-5-(1H-imidazol-1-ylmethyl)-2-pyrrolidinone (MM1): A novel antihypertensive agent. Med. Chem. Res., 2012, 21, 321-324.
[http://dx.doi.org/10.1007/s00044-010-9536-6]
[11]
Najera, C.; Yus, M. Pyroglutamic acid: A versatile building block in asymmetric synthesis. Tetrahedron Asymmetry, 1999, 10, 2245-2303.
[http://dx.doi.org/10.1016/S0957-4166(99)00213-X]
[12]
Panday, S.K.; Prasad, J.; Dikshit, D.K. Pyroglutamic acid: A unique chiral synthon. Tetrahedron Asymmetry, 2009, 20, 1581-1632.
[http://dx.doi.org/10.1016/j.tetasy.2009.06.011]
[13]
Stefanucci, A.; Novellino, E.; Costante, R.; Mollica, A. Pyroglutamic acid derivatives: Building blocks for drug discovery. Heterocycles, 2014, 89, 1801-1825.
[http://dx.doi.org/10.3987/REV-14-800]
[14]
Carlson, N.R. Psychology: The Science of Behavior; Allyn and Bacon: Boston, 1984.
[15]
Carlson, N.R. Behavioral Physiology; Continental: New York, 1982.
[16]
Moloney, M.G. Excitatory amino acids. Nat. Prod. Rep., 1998, 15(2), 205-219.
[http://dx.doi.org/10.1039/a815205y] [PMID: 9586226]
[17]
Fritsch, B.; Reis, J.; Gasior, M.; Kaminski, R.M.; Rogawski, M.A. Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis. J. Neurosci., 2014, 34(17), 5765-5775.
[http://dx.doi.org/10.1523/JNEUROSCI.5307-13.2014] [PMID: 24760837]
[18]
(a) Cossy, J.; Cases, M.; Pardo, D. G. Approaches to a synthesis of α-kainic acid. Tetrahedron, 1999, 55, 6153-6166.
(b) Hanessian, S.; Ninkovic, S. Stereoselective synthesis of (−)-α-Kainic acid and (+)-α-allokainic acid via trimethylstannyl-mediated radical carbocyclization and oxidative destannylation. J. Org. Chem., 1996, 61, 5418-5424.
(c) Baldwin, J.E.; Moloney, M. G.; Parsous, A. F. Enantioselective kainoid synthesis by cobalt-mediated cyclisation of an amino acid derivative. Tetrahedron, 1990, 46, 7263-7282.
[19]
Aráoz, R.; Molgó, J.; Tandeau de Marsac, N. Neurotoxic cyanobacterial toxins. Toxicon, 2010, 56(5), 813-828.
[http://dx.doi.org/10.1016/j.toxicon.2009.07.036] [PMID: 19660486]
[20]
Botana, L.M.; James, K.; Crowley, J.; Duphard, J.; Lehane, M.; Furey, A. Phycotoxins. ChemBioChem, 2007, 12, 858-862.
[21]
Peterson, J.S.; Fels, G.; Rapoport, H. Chirospecific synthesis of (+) and (−)-anatoxin a. J. Am. Chem. Soc., 1984, 106, 4539-4547.
[http://dx.doi.org/10.1021/ja00328a040]
[22]
Gray, D.O.; Fowden, L. 4-Methyleneproline: A new naturally occurring proline derivative. Nature, 1962, 193, 1285-1286.
[http://dx.doi.org/10.1038/1931285a0] [PMID: 13901295]
[23]
Gray, D.O.; Fowden, L. Isolation of 4-methylene-DL-proline from Eriobotrya japonica. Phytochemistry, 1972, 11, 745-750.
[http://dx.doi.org/10.1016/0031-9422(72)80042-6]
[24]
Tristram, H.; Neale, S. The activity and specificity of the proline permease in wild-type and analogue-resistant strains of Escherichia coli. J. Gen. Microbiol., 1968, 50(1), 121-137.
[http://dx.doi.org/10.1099/00221287-50-1-121] [PMID: 4865475]
[25]
Manfre, F.; Kern, J.M.; Beillmann, J.F. Syntheses of proline analogs as potential mechanism-based inhibitors of proline dehydrogenase: 4-Methylene-L-, (E)- and (Z)-4-(fluoromethylene)-L-, cis and trans-5-ethynyl-(+)-, and cis- and trans- 5-vinyl-L-proline. J. Org. Chem., 1992, 57, 2060-2065.
[http://dx.doi.org/10.1021/jo00033a029]
[26]
Tritsch, D.; Mawlawi, H.; Biellmann, J.F. Mechanism-based inhibition of proline dehydrogenase by proline analogues. Biochim. Biophys. Acta, 1993, 1202(1), 77-81.
[http://dx.doi.org/10.1016/0167-4838(93)90065-Y] [PMID: 8373828]
[27]
Tozuka, Z.; Takaya, T. Tennen Yuki Kagobutsu Toronkai koen Yoshishu. Chem. Abstr, 1981, 24, 552-559.
[28]
Natarajan, S.I.; Ondetti, M.A. US 304148. Chem. Abstr, 1983, 3, 233-339.
[29]
Panday, S.K.; Griffart-Brunet, D.; Langlois, N. A short and efficient synthesis of (S)-4-methylene proline benzyl ester from (S)-pyroglutamic acid. Tetrahedron Lett., 1994, 35, 6673-6676.
[http://dx.doi.org/10.1016/S0040-4039(00)73465-4]
[30]
Shinagawa, S.; Kasahara, F.; Wada, Y.; Harada, S.; Asai, M. Structures of bulgecins, bacterial metabolites with bulge-inducing activity. Tetrahedron, 1984, 40, 3465-3470.
[http://dx.doi.org/10.1016/S0040-4020(01)91497-8]
[31]
Shinagawa, S.; Maki, M.; Kintaka, K.; Imada, A.; Asai, M. Isolation and characterization of bulgecins, new bacterial metabolites with bulge-inducing activity. J. Antibiot. (Tokyo), 1985, 38(1), 17-23.
[http://dx.doi.org/10.7164/antibiotics.38.17] [PMID: 3918981]
[32]
Cooper, R.; Unger, S. Novel potentiators of beta-lactam antibiotics. Structures of SQ 28504 and SQ 28546. J. Org. Chem., 1986, 51, 3942-3946.
[http://dx.doi.org/10.1021/jo00371a005]
[33]
Wakamiya, T.; Yamanoi, K.; Nishikawa, L.; Shiba, T. Synthe-sis of bulgecinine: a new amino acid in bulgecins. Tetrahedron Lett., 1985, 26, 4759-4760.
[http://dx.doi.org/10.1016/S0040-4039(00)94943-8]
[34]
Bashyal, B.; Chow, H-F.; Fleet, G.W.J. Enantiospecific syn-theses of 2S, 3R, 4R, 5S- trihydroxypipecolic acid, 2R,3R,4R,5Strihydroxypipecolic acid, 2S,4S,5S-dihydroxypipecolic acid, and bulgecinine from D-glucuronolactone. Tetrahedron Lett., 1986, 27, 3205-3208.
[http://dx.doi.org/10.1016/s0040-4039(00)84755-3]
[35]
Bashyal, B.; Chow, H-F.; Fleet, G.W.J. Synthesis of 2s, 4s, 5s - dihydroxypipecolic acid and bulgecinine [2s,4s,5r-4-hydroxy-5- (hydroxymethyl)proline] from d-glucuronolactone, a strategy for the synthesis of 2s,4s-4-hydroxy-α-amino acids. Tetrahedron, 1987, 43, 423-430.
[http://dx.doi.org/10.1016/S0040-4020(01)89973-7]
[36]
Ohta, T.; Hosoi, A.; Nozoe, S. Stereoselective hydroxylation of Ncarbamoyl-L-pyroglutamate. Synthesis of (−)- bulgecinine. Tetrahedron Lett., 1988, 29, 329-332.
[http://dx.doi.org/10.1016/S0040-4039(00)80087-8]
[37]
Barett, A.G.M.; Pilipauskas, D. Electrochemical oxidation of proline derivatives: Total syntheses of bulgecinine and bulgecin C. J. Org. Chem., 1991, 56, 2787-2800.
[http://dx.doi.org/10.1021/jo00008a040]
[38]
Hirai, Y.; Terada, T.; Amemiya, Y.; Mamose, T. An efficient synthesis of (-)-bulgecinine. Tetrahedron Lett., 1992, 33, 7893-7894.
[http://dx.doi.org/10.1016/S0040-4039(00)74771-X]
[39]
Madau, A.; Porzi, G.; Sandri, S. Stereoselective synthesis of unnatural aminoacids cis-4-hydroxyproline and bulgecinine. Tetrahedron Asymmetry, 1996, 7, 825-830.
[http://dx.doi.org/10.1016/0957-4166(96)00079-1]
[40]
Yuasa, Y.; Ando, J.; Shibuya, S. Diastereoselective synthesis of 2,5-disubstituted 3-hydroxypyrrolidine and 2,6-disubstituted 3-hydroxypiperidine derivatives by radical cy-clisation; synthesis of (+)-bulgecinine and (–)-desoxoprosopinine. J. Chem. Soc., Perkin Trans. 1, 1996, 793-802.
[http://dx.doi.org/10.1039/P19960000793]
[41]
Panday, S.K.; Langlois, N. An efficient straightforward synthesis of (-)-bulgecinine. Synth. Commun., 1997, 27, 1373-1384.
[http://dx.doi.org/10.1080/00397919708006067]
[42]
Banga, N.R.; Welter, A.; Jadot, J.; Casimir, J. Un nouvel acide amine isole de Lycoperdon perlatum. Phytochemistry, 1979, 18, 482-484.
[http://dx.doi.org/10.1016/S0031-9422(00)81892-0]
[43]
Lamotte, J.; Oleksyn, B.; Dupont, L.; Didberg, O.; Campsteyn, H.; Vermeire, M. The crystal and molecular structure of 3-[(5 S)-5-carboxy-2-oxotetrahydrofur-5-yl]- (2 S)-alanine (lycoperdic acid). Acta Crystallogr., 1978, B34, 3635-3638.
[http://dx.doi.org/10.1107/S0567740878011772]
[44]
Ohfune, Y.; Shinada, T. Enantio‐ and diastereoselective construction of α,α‐disubstituted α‐amino acids for the synthesis of biologically active compounds. Eur. J. Org. Chem., 2005, 24, 5127-5143.
[http://dx.doi.org/10.1002/ejoc.200500434]
[45]
Tamura, O.; Shiro, T.; Ogasawara, M.; Toyao, A.; Ishibashi, H. Stereoselective syntheses of 4-hydroxy 4-substituted glutamic acids. J. Org. Chem., 2005, 70(12), 4569-4577.
[http://dx.doi.org/10.1021/jo040296h] [PMID: 15932291]
[46]
Sakai, R.; Kamiyla, H.; Murata, M.; Shimamoto, K. Dysiherbaine: A new neurotoxic amino acid from the Micronesian marine sponge Dysidea herbacea. J. Am. Chem. Soc., 1997, 119, 4112-4116.
[http://dx.doi.org/10.1021/ja963953z]
[47]
Sakai, R.; Koike, T.; Sasaki, M.; Shimamoto, K.; Oiwa, C.; Yano, A.; Suzuki, K.; Tachibana, K.; Kamiya, H. Isolation, structure determination, and synthesis of neodysiherbaine A, a new excitatory amino acid from a marine sponge. Org. Lett., 2001, 3(10), 1479-1482.
[http://dx.doi.org/10.1021/ol015798l] [PMID: 11388846]
[48]
Sanders, J.M.; Ito, K.; Settimo, L.; Pentikäinen, O.T.; Shoji, M.; Sasaki, M.; Johnson, M.S.; Sakai, R.; Swanson, G.T. Divergent pharmacological activity of novel marine-derived excitatory amino acids on glutamate receptors. J. Pharmacol. Exp. Ther., 2005, 314(3), 1068-1078.
[http://dx.doi.org/10.1124/jpet.105.086389] [PMID: 15914675]
[49]
Sakai, R.; Swanson, G.T.; Shimamoto, K.; Green, T.; Contractor, A.; Ghetti, A.; Tamura-Horikawa, Y.; Oiwa, C.; Kamiya, H. Pharmacological properties of the potent epileptogenic amino acid dysiherbaine, a novel glutamate receptor agonist isolated from the marine sponge Dysidea herbacea. J. Pharmacol. Exp. Ther., 2001, 296(2), 650-658.
[PMID: 11160654]
[50]
Swanson, G.T.; Green, T.; Sakai, R.; Contractor, A.; Che, W.; Kamiya, H.; Heinemann, S.F. Differential activation of individual subunits in heteromeric kainate receptors. Neuron, 2002, 34(4), 589-598.
[http://dx.doi.org/10.1016/S0896-6273(02)00676-1] [PMID: 12062042]
[51]
Cohen, J.L.; Chamberlin, A.R. Diastereoselective synthesis of glutamate-appended oxolane rings: Synthesis of (s)-(+)-lycoperdic acid. J. Org. Chem., 2007, 72(24), 9240-9247.
[http://dx.doi.org/10.1021/jo7017137] [PMID: 17975930]
[52]
Feling, R.H.; Buchanan, G.O.; Mincer, T.J.; Kauffman, C.A.; Jensen, P.R.; Fenical, W.; Salinosporamide, A. Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angew. Chem. Int. Ed. Engl., 2003, 42(3), 355-357.
[http://dx.doi.org/10.1002/anie.200390115] [PMID: 12548698]
[53]
Chauhan, D.; Catley, L.; Li, G.; Podar, K.; Hideshima, T.; Velankar, M.; Mitsiades, C.; Mitsiades, N.; Yasui, H.; Letai, A.; Ovaa, H.; Berkers, C.; Nicholson, B.; Chao, T.H.; Neuteboom, S.T.; Richardson, P.; Palladino, M.A.; Anderson, K.C. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell, 2005, 8(5), 407-419.
[http://dx.doi.org/10.1016/j.ccr.2005.10.013] [PMID: 16286248]
[54]
Caubert, V.; Masse, J.; Retailleau, P.; Langlois, N. Stereoselec-tive formal synthesis of the potent proteasome inhibitor. Salinosporamide A. Tetrahedron Lett., 2007, 48, 381-384.
[http://dx.doi.org/10.1016/j.tetlet.2006.11.087]
[55]
Reddy, L.R.; Saravanan, P.; Corey, E.J. A simple stereocontrolled synthesis of salinosporamide A. J. Am. Chem. Soc., 2004, 126(20), 6230-6231.
[http://dx.doi.org/10.1021/ja048613p] [PMID: 15149210]
[56]
Reddy, L.R.; Fournier, J-F.; Reddy, B.V.S.; Corey, E.J. New synthetic route for the enantioselective total synthesis of salinosporamide A and biologically active analogues. Org. Lett., 2005, 7(13), 2699-2701.
[http://dx.doi.org/10.1021/ol0508734] [PMID: 15957925]
[57]
Endo, A.; Danishefsky, S.J. Total synthesis of salinosporamide A. J. Am. Chem. Soc., 2005, 127(23), 8298-8299.
[http://dx.doi.org/10.1021/ja0522783] [PMID: 15941259]
[58]
Mulholland, N.P.; Pattenden, G.; Walters, I.A.S. A concise total synthesis of salinosporamide A. Org. Biomol. Chem., 2006, 4(15), 2845-2846.
[http://dx.doi.org/10.1039/b607109k] [PMID: 16855730]
[59]
Ling, T.; Macherla, V.R.; Manam, R.R.; McArthur, K.A.; Potts, B.C. Enantioselective total synthesis of (−)-salinosporamide A. Org. Lett., 2007, 9(12), 2289-2292.
[http://dx.doi.org/10.1021/ol0706051] [PMID: 17497868]
[60]
Langlois, N.; Le Nguyen, B.K. Diastereoselective syntheses of deoxydysibetaine, dysibetaine, and its 4-epimer. J. Org. Chem., 2004, 69(22), 7558-7564.
[http://dx.doi.org/10.1021/jo040216+] [PMID: 15497982]
[61]
Cubert, V.; Langlois, N. Studies toward the synthesis of salinosporamide A, a potent proteasome inhibitor. Tetrahedron Lett., 2006, 47, 4473-4475.
[http://dx.doi.org/10.1016/j.tetlet.2006.04.070]
[62]
Lin, G-J.; Huang, P-Q. A concise and fully selective synthesis of the ant venom alkaloid (3S,5R,8S,9S)-3-butyl-5-propyl-8-hydroxyindolizidine. Org. Biomol. Chem., 2009, 7(21), 4491-4495.
[http://dx.doi.org/10.1039/b912190k] [PMID: 19830300]
[63]
Jin, Z.; Li, S.P.; Wang, Q.M.; Huang, R.Q. A concise total synthesis of S-(+)-tylophorine. Chin. Chem. Lett., 2004, 15, 1164.
[64]
Hanessian, S.; Margarita, R.; Hall, A.; Johnstone, S.; Tremblay, M.; Parlanti, L. Total synthesis and structural confirmation of the marine natural product Dysinosin A: a novel inhibitor of thrombin and Factor VIIa. J. Am. Chem. Soc., 2002, 124(45), 13342-13343.
[http://dx.doi.org/10.1021/ja0208153] [PMID: 12418860]
[65]
Ishibashi, M. Ohizumi,Y.; Sasaki, T.; Nakamura, H.; Hirata, Y.; Kobayashi, J. Pseudodistomins A and B, novel antineo-plastic piperdine alkaloids with calmodulin antagonistic activity from the Okinawan tunicate Pseudodistoma kanoko. J. Org. Chem., 1987, 52, 450-453.
[http://dx.doi.org/10.1021/jo00379a028]
[66]
Ishibashi, M.; Deki, K.; Kobayashi, J. Revised structure of Pseudodistomin A, a piperidine alkaloid isolated from the Okinawan tunicate Pseudodistoma kanoko. J. Nat. Prod., 1995, 58, 804-806.
[http://dx.doi.org/10.1021/np50119a028]
[67]
Kobayashi, J. Naitoh, K.; Doi, Y.; Deki, K.; Ishibashi, M.; Pseudodistomin C, a new piperidine alkaloid with unusual absolute configuration from the Okinawan tunicate Pseudodistoma kanoko. J. Org. Chem., 1995, 60, 6941-6945.
[http://dx.doi.org/10.1021/jo00126a053]
[68]
Freyer, A.J.; Patil, A.D.; Killmer, L.; Troupe, N.; Mentzer, M.; Carte, B.; Faucette, L.; Johnson, R.K. Three new pseudodistomins, piperidine alkaloids from the ascidian Pseudodistoma megalarva. J. Nat. Prod., 1997, 60(10), 986-990.
[http://dx.doi.org/10.1021/np9701438] [PMID: 9358640]
[69]
Kobayashi, J. Ishibashi, M.; Sphingosine-related marine alkaloids: Cyclic amino alcohols. Heterocycles, 1996, 42, 943-970.
[http://dx.doi.org/10.3987/REV-95-SR6]
[70]
Ninomiya, I.; Kiguchi, T.; Naito, T. Chapter 8 Pseudodistomins: Structure, synthesis, and pharmacology. Alkaloids Chem. Biol., 1998, 50, 317-342.
[71]
Langlois, N. Stereoselective formal synthesis of pseudodistomin C. Org. Lett., 2002, 4(2), 185-187.
[http://dx.doi.org/10.1021/ol010221p] [PMID: 11796046]
[72]
Doi, Y.; Ishbashi, M.; Kobayashi, J. Total synthesis of Pseudodistomin C, a sphingosine-related piperidine alkaloid from tunicate Pseudodistoma kanoko. Tetrahedron, 1996, 52, 4573-4580.
[http://dx.doi.org/10.1016/0040-4020(96)00137-8]
[73]
Schwartz, R.E.; Helms, G.L.; Bolessa, E.A.; Wilson, K.E.; Giacobbe, R.A.; Tkacz, J.S.; Bills, G.F.; Liesch, J.M.; Zink, D.L.; Curotto, J.E.; Pramanik, B.; Onishi, J.C. Pramanicin, a novel antimicrobial agent from a fungal fermentation. Tetrahedron, 1994, 50, 1675-1686.
[http://dx.doi.org/10.1016/S0040-4020(01)80843-7]
[74]
Barett, A. G. M.; Smith, M. L. Total synthesis of (+)-pramanicin and stereochemical elucidation of the natural product; Chem. Comm, 1999, 133-134.
[75]
Barett, A.G.M.; Head, J.; Smith, M.L.; Stock, N.S.; White, A.J.P.; Williams, D.J. Fleming-Tamao oxidation and masked hydroxyl functionality: Total synthesis of (+)-pramanicin and structural elucidation of the antifungal natural product (−)-pramanicin. J. Org. Chem., 1999, 64, 6005-6018.
[http://dx.doi.org/10.1021/jo9905672]
[76]
Kutuk, O.; Pedrech, A.; Harrison, P.; Basaga, H. Pramanicin induces apoptosis in Jurkat leukemia cells: A role for JNK, p38 and caspase activation. Apoptosis, 2005, 10(3), 597-609.
[http://dx.doi.org/10.1007/s10495-005-1894-z] [PMID: 15909121]
[77]
Bodur, C.; Kutuk, O.; Karsli-Uzunbas, G.; Isimjan, T.T.; Harrison, P.; Basaga, H. Pramanicin analog induces apoptosis in human colon cancer cells: Critical roles for Bcl-2, Bim, and p38 MAPK signaling. PLoS One, 2013, 8(2), e56369.
[http://dx.doi.org/10.1371/journal.pone.0056369] [PMID: 23441183]
[78]
Bailey, J.H.; Cherry, D.T.; Crapnell, K.M.; Moloney, M.G.; Shim, S.B.; Bamford, M.; Lamont, R.B. Functionalised pyrrol-idinones derived from (S)-pyroglutamic acid by cycloaddition reactions. Tetrahedron, 1997, 53, 11731-11744.
[http://dx.doi.org/10.1016/S0040-4020(97)00740-0]
[79]
Dyer, J.; Keelings, S.; King, A.; Moloney, M.G. Pyrroli-dinones derived from (S)-pyroglutamic acid. Part 2. Conformationally constrained kainoid analogues. J. Chem. Soc. Per-kin Trans., 2000, I, 2793-2804.
[http://dx.doi.org/10.1039/b002001j]
[80]
Bailey, J.H.; Cherry, D.; Dyer, J.; Moloney, M.G.; Bamford, M.J.; Keeling, S.; Lamont, R.B. Pyrrolidinones derived from (S)-pyroglutamic acid, Part 1. Conformationally constrained glutamate. J. Chem. Soc. Perkin Trans., 2000, I, 2783-2792.
[http://dx.doi.org/10.1039/b001999m]
[81]
Chan, P.W.H.; Cottrell, I.F.; Moloney, M.G. Pyrrolidinones derived from (S)-pyroglutamic acid. Part 3. β -Aminopyrrolidinones. J. Chem. Soc. Perkin Trans., 2001, I, 2997-3006.
[http://dx.doi.org/10.1039/b106782f]
[82]
Langlois, N. Short stereocontrolled synthesis of (2S,3S,4R)-3,4-dihydroxyglutamic acid. Tetrahedron Lett., 1999, 40, 8801-8803.
[http://dx.doi.org/10.1016/S0040-4039(99)01873-0]
[83]
D.; Langlois, N.; A short diastereoselective synthesis of the natural (2R, 3R, 4R)-2-hydroxymethyl-3, 4-dihydroxypyrrolidine. Tetrahedron Lett., 1994, 35, 2889-2890.
[http://dx.doi.org/10.1016/S0040-4039(00)76651-2]
[84]
Tan, S.W.B.; Chai, C.L.L.; Moloney, M.G.; Thompson, A.L. Synthesis of mimics of pramanicin from pyroglutamic acid and their antibacterial activity. J. Org. Chem., 2015, 80(5), 2661-2675.
[http://dx.doi.org/10.1021/jo502810b] [PMID: 25647715]
[85]
Saliou, C.; Fleurant, A.; Celerier, J.P.; Lhommet, G. Total synthesis of (+) monomorine I from chiral cyclic β-enamino ester. Tetrahedron Lett., 1991, 32, 3365-3368.
[http://dx.doi.org/10.1016/S0040-4039(00)92707-2]
[86]
Nguyen, B.K.L.; Langlois, N. Concise syntheses of racemic and enantiopure deoxydysibetaine. Tetrahedron Lett., 2003, 44, 5961-5963.
[http://dx.doi.org/10.1016/S0040-4039(03)01505-3]
[87]
Aggarwal, V.K.; Astle, C.J.; Rogers-Evans, M. A concise asymmetric route to the bridged bicyclic tropane alkaloid ferruginine using enyne ring-closing metathesis. Org. Lett., 2004, 6(9), 1469-1471.
[http://dx.doi.org/10.1021/ol049665m] [PMID: 15101769]
[88]
Olivo, H.F.; Tovar-Miranda, R.; Barragán, E. Synthesis of (-)-stemoamide using a stereoselective anti-aldol step. J. Org. Chem., 2006, 71(8), 3287-3290.
[http://dx.doi.org/10.1021/jo052364l] [PMID: 16599632]
[89]
Torssell, S.; Wanngren, E.; Somfai, P. Total synthesis of (-)-stemoamide. J. Org. Chem., 2007, 72(11), 4246-4249.
[http://dx.doi.org/10.1021/jo070498o] [PMID: 17451274]
[90]
Yoritate, M.; Takahashi, Y.; Tajima, H.; Ogihara, C.; Yokoyama, T.; Soda, Y.; Oishi, T.; Sato, T.; Chida, N. Unified total synthesis of stemoamide-type alkaloids by chemoselective assembly of fivemembered building blocks. J. Am. Chem. Soc., 2017, 139(50), 18386-18391.
[http://dx.doi.org/10.1021/jacs.7b10944] [PMID: 29179540]
[91]
Kato, A.; Adachi, I.; Miyauchi, M.; Ikeda, K.; Komae, T.; Kizu, H.; Kameda, Y.; Watson, A.A.; Nash, R.J.; Wormald, M.R.; Fleet, G.W.J.; Asano, N. Polyhydroxylated pyrrolidine and pyrrolizidine alkaloids from Hyancinthoides non-scripta and Scilla campanulata. Carbohydr. Res., 1999, 316(1-4), 95-103.
[http://dx.doi.org/10.1016/S0008-6215(99)00043-9] [PMID: 10515698]
[92]
Reddy, P.V.; Smith, J.; Kamath, A.; Jamet, H.; Veyron, A.; Koos, P.; Philouze, C.; Greene, A.E.; Delair, P. Asymmetric approach to hyacinthacines B1 and B2. J. Org. Chem., 2013, 78(10), 4840-4849.
[http://dx.doi.org/10.1021/jo400386f] [PMID: 23557153]
[93]
Sengoku, T.; Satoh, Y.; Oshima, M.; Takahashi, M.; Yoda, H. First asymmetric synthesis of pyrrolizidine alkaloids, (+)-hyacinthacine B1 and (+)-B2. Tetrahedron, 2008, 64, 8052-8058.
[http://dx.doi.org/10.1016/j.tet.2008.06.078]
[94]
Seigler, D.S. Pyrrolizidine; Quinolizidine, and Indolizidine Alkaloids. Plant Secondary Metabolism; Springer Science and Business Media: New York, 1998, pp. 546-567.
[95]
Toyooka, N.; Zhou, D.; Nemoto, H.; Tezuka, Y.; Kadota, S.; Jones, T.H.; Garraffo, H.M.; Spande, T.F.; Daly, J.W. First enantioselective synthesis of a hydroxyindolizidine alkaloid from the Ant Myrmicaria melanogaster. Synlett, 2008, 12, 1894-1896.
[http://dx.doi.org/10.1055/s-2008-1078502]
[96]
Segraves, N.L.; Crews, P. A Madagascar sponge Batzella sp. as a source of alkylated iminosugars. J. Nat. Prod., 2005, 68(1), 118-121.
[http://dx.doi.org/10.1021/np049763g] [PMID: 15679333]
[97]
Wierzejska, J.; Motogoe, S.; Makino, Y.; Sengoku, T.; Takahashi, M.; Yoda, H. A new approach toward the total synthesis of (+)-batzellaside B. Beilstein J. Org. Chem., 2012, 8, 1831-1838.
[http://dx.doi.org/10.3762/bjoc.8.210] [PMID: 23209519]
[98]
Wierzejska, J.; Ohshima, M.; Inuzuka, T.; Sengoku, T.; Takahashi, M.; Yoda, H. Total synthesis and absolute stereo-chemistry of (+)-batzellaside B and its C8-epimer, a new class of piperidine alkaloids from the sponge Batzella sp. Tetrahedron Lett., 2011, 52, 1173-1175.
[http://dx.doi.org/10.1016/j.tetlet.2011.01.018]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version309msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[04:25:34] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[04:25:34] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[04:25:34] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (93.86ms)time
  • Application (215ms)time
  • 1 x Application (69.6%)
    215ms
    1 x Booting (30.4%)
    93.86ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated143ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('58953283','',1,1740457534,1740457534) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740457534
      1.07msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('58953283','/article/100848',1,1740457534,1740457534)
      1.25msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 58953283 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 58953283) limit 1
      11.27msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 58953283
      • 1: 58953283
      • 2: 58953283
      • 3: 58953283
      • 4: 58953283
      • 5: 58953283
      • 6: 58953283
      • 7: 58953283
      • 8: 58953283
      • 9: 58953283
      • 10: 58953283
      • 11: 58953283
      • 12: 58953283
      • 13: 58953283
      • 14: 58953283
      • 15: 58953283
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=100848
      680μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 45 limit 1
      810μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 45
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=45) and sj.journal_id!=45 group by `j`.`nid`) as `aggregate_table`
      600μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=45) and sj.journal_id!=45 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      530μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=45) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      790μsalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=45) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      720μsalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '100848'
      790μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 100848
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '100848'
      3.49msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 100848
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '100848' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.57msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 100848
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      230μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 45 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      23.84msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 45 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      7.33msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 45 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      4.41msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 100848 limit 1
      200μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 100848
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 100848 and content_type = 'article' order by status desc limit 1
      280μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 467 and content_id!=100848 and cd.content_type = 'article' order by rand() limit 20
      57.78msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 174928 limit 1
      290μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 174928
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      230μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'MROC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      270μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: MROC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '100848' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9972' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      330μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2719' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      280μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2719) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2719) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2719)
      15.86msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9972) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9972) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9972)
      620μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 100848) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 100848) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 58953283 and j.to_ip >=58953283 )) and ((j.from_date <= 1740457534 and j.to_date >= 1740457534 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 100848)
      700μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '626' and is_uploaded = 1 and issue_id = 9972 order by cast(first_page as SIGNED) desc limit 1
      540μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 626
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '646' and is_uploaded = 1 and issue_id = 9972 order by cast(first_page as SIGNED) asc limit 1
      390μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 646
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      180μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      240μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 100848 limit 1
      2.35msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 100848
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 45 and `b`.`banner_from_date` <= 1740457534 and `b`.`banner_to_date` >= 1740457534 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.09msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 45
      • 3: 1740457534
      • 4: 1740457534
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 45 and `b`.`banner_from_date` <= 1740457534 and `b`.`banner_to_date` >= 1740457534 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 45
      • 3: 1740457534
      • 4: 1740457534
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='44404b804fb3ef6858f7c2edc10bbfd7'
      210μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        LhMoYfD0MiAOE4RwimUoKSas9I5Oasgi6SnaIGMN
        uc_cart_id
        44404b804fb3ef6858f7c2edc10bbfd7
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/100848" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/100848
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Ik9OWlVCWGl4NkFpRWhuYVNhaEQvWUE9PSIsInZhbHVlIjoiTEFDRGxKNWJuYzFqWFc0VUFWVDNDTk1vN0VOWnVMdDVIeWxZVUlFQUlnUT0iLCJtYWMiOiJjN2I3ZTE1MGQxOGJjYWNlZWRhN2NmMzRmZjhkY2M2ZWMwNWM5YmFlYzYyNmNhODk5MzdlMzU3ZmZmNzA2MzY0IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ik9OWlVCWGl4NkFpRWhuYVNhaEQvWUE9PSIsInZhbHVlIjoiTEFDRGxKNWJuYzFqWFc0VUFWVDNDTk1vN0VOWnVMdDVIeWxZVUlFQUlnUT0iLCJtYWMiOiJjN2I3ZTE1MGQxOGJj" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 04:25:34 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkljU0hQaEpnYm5aS1ZaQUd1dUhmZEE9PSIsInZhbHVlIjoicGUxWXlueWxhL296R0VNM0p0RktyUEhWT3hYWXZZWHVyc3ZRcVJzM3d6K2E1enVmSUFqUEpNYThFOXVPajJES1ZVbVVCa3VNWUFBbm4xU3hCZXRSVmdXaGUrTUhxU3JpYjNnMUNkZkVYSVhoSitkc3duaVpsZDM0OGYyRkhYV0kiLCJtYWMiOiI4YTVkMWJjNzM2MTI4Zjg0NGViOTlmM2RlMTMwYTMyNmY4M2I1MDcxZTAzOWE5MjZmNjBjZDU3Y2E2MzdmYWRlIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 16:25:34 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkljU0hQaEpnYm5aS1ZaQUd1dUhmZEE9PSIsInZhbHVlIjoicGUxWXlueWxhL296R0VNM0p0RktyUEhWT3hYWXZZWHVyc3ZRcVJzM3d6K2E1enVmSUFqUEpNYThFOXVPajJES1ZVbVVCa" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFla205UWM5bzE4bUY5WVlLUFNxaGc9PSIsInZhbHVlIjoiL2FKZmhBcm1Kbm9UWTZIWUJIdXgvRkkvY3hBd0VrVHJFQUtqM1gwZUZlQkVlQ0Z5SDFFS0hVeG1JRG5uQUNwZDI5N2FpTExxdkFpQ2pxWUVvbzRVdlJ4MTBBNTNCcEVORkVhc3orVTFSUzZNaXBvdnN0OXFkZHhOYVFreVovVzkiLCJtYWMiOiI5ZmRjZjI0Njc0MGJiNjQ4NGFhOTg0ZmMzM2VmMzIzYzEyNGI2NmM2OWRmODNhMTU5MGJlYWUzNjgzMDlmYjBjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImFla205UWM5bzE4bUY5WVlLUFNxaGc9PSIsInZhbHVlIjoiL2FKZmhBcm1Kbm9UWTZIWUJIdXgvRkkvY3hBd0VrVHJFQUtqM1gwZUZlQkVlQ0Z5SDFFS0hVeG1" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkljU0hQaEpnYm5aS1ZaQUd1dUhmZEE9PSIsInZhbHVlIjoicGUxWXlueWxhL296R0VNM0p0RktyUEhWT3hYWXZZWHVyc3ZRcVJzM3d6K2E1enVmSUFqUEpNYThFOXVPajJES1ZVbVVCa3VNWUFBbm4xU3hCZXRSVmdXaGUrTUhxU3JpYjNnMUNkZkVYSVhoSitkc3duaVpsZDM0OGYyRkhYV0kiLCJtYWMiOiI4YTVkMWJjNzM2MTI4Zjg0NGViOTlmM2RlMTMwYTMyNmY4M2I1MDcxZTAzOWE5MjZmNjBjZDU3Y2E2MzdmYWRlIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 16:25:34 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkljU0hQaEpnYm5aS1ZaQUd1dUhmZEE9PSIsInZhbHVlIjoicGUxWXlueWxhL296R0VNM0p0RktyUEhWT3hYWXZZWHVyc3ZRcVJzM3d6K2E1enVmSUFqUEpNYThFOXVPajJES1ZVbVVCa" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFla205UWM5bzE4bUY5WVlLUFNxaGc9PSIsInZhbHVlIjoiL2FKZmhBcm1Kbm9UWTZIWUJIdXgvRkkvY3hBd0VrVHJFQUtqM1gwZUZlQkVlQ0Z5SDFFS0hVeG1JRG5uQUNwZDI5N2FpTExxdkFpQ2pxWUVvbzRVdlJ4MTBBNTNCcEVORkVhc3orVTFSUzZNaXBvdnN0OXFkZHhOYVFreVovVzkiLCJtYWMiOiI5ZmRjZjI0Njc0MGJiNjQ4NGFhOTg0ZmMzM2VmMzIzYzEyNGI2NmM2OWRmODNhMTU5MGJlYWUzNjgzMDlmYjBjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImFla205UWM5bzE4bUY5WVlLUFNxaGc9PSIsInZhbHVlIjoiL2FKZmhBcm1Kbm9UWTZIWUJIdXgvRkkvY3hBd0VrVHJFQUtqM1gwZUZlQkVlQ0Z5SDFFS0hVeG1" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "LhMoYfD0MiAOE4RwimUoKSas9I5Oasgi6SnaIGMN" "uc_cart_id" => "44404b804fb3ef6858f7c2edc10bbfd7" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/100848" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 04:25:34GET/article/100848314371