“…Except for the ion peak at m/z 204.071 [M-H] - , all ion peaks generated a predicted molecular formula and the putatively identified bioactive metabolites contained both nitrogen and oxygen with RDBEs between 8 to 23. Using Chemspider, the predicted molecular formulas with the search term “antimicrobials”, synthetically produced compounds were dereplicated, which included 8-substituted-2’-deoxyguanosines ( 1 ) [70], glycosyl amides ( 2 ) [71], benzofurans ( 3 , 9 ) [72, 73], diphenyl-4-hydroxypiperidines ( 5 ) [74], spiro heterocycles ( 6 ) [75], benzimidazoles ( 7 ) [76] and biphenyls ( 8 ) [77]. N_2020 or compound 7 was dereplicated as an antimicrobial synthetic benzimidazole congener [76] and was a metabolite determined to be putatively specific against E .…”
Literature surveys, taxonomical differences, and bioassay results have been utilized in the discovery of new natural products to aid in Actinomycetes isolate-selection. However, no or less investigation have been done on establishing the differences in metabolomic profiles of the isolated microorganisms. The study aims to utilise bioassay- and metabolomics-guided tools that included dereplication study and multivariate analysis of the NMR and mass spectral data of microbial extracts to assist the selection of isolates for scaling-up the production of antimicrobial natural products. A total of 58 actinomycetes were isolated from different soil samples collected from Ihnasia City, Egypt and screened for their antimicrobial activities against indicator strains that included Bacillus subtilis, Escherichia coli, methicillin-resistant Staphylococcus aureus and Candida albicans. A number of 25 isolates were found to be active against B. subtilis and/or to at least one of the tested indicator strains. Principal component analyses showed chemical uniqueness for four outlying bioactive actinomycetes extracts. In addition, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and dereplication study led us to further select two outlying anti-MRSA active isolates MS.REE.13 and 22 for scale-up work. MS.REE.13 and 22 exhibited zones of inhibition at 19 and 13 mm against MRSA, respectively. A metabolomics-guided approach provided the steer to target the bioactive metabolites (P<0.01) present in a crude extract or fraction even at nanogram levels but it was a challenge that such low-yielding bioactive natural products would be feasible to isolate. Validated to occur only on the active side of OPLS-DA loadings plot, the isolated compounds exhibited medium to weak antibiotic activity with MIC values between 250 and 800 μM. Two new compounds, P_24306 (C10H13N2) and N_12799 (C18H32O3) with MICs of 795 and 432 μM, were afforded from the scale-up of MS.REE. 13 and 22, respectively.
“…Except for the ion peak at m/z 204.071 [M-H] - , all ion peaks generated a predicted molecular formula and the putatively identified bioactive metabolites contained both nitrogen and oxygen with RDBEs between 8 to 23. Using Chemspider, the predicted molecular formulas with the search term “antimicrobials”, synthetically produced compounds were dereplicated, which included 8-substituted-2’-deoxyguanosines ( 1 ) [70], glycosyl amides ( 2 ) [71], benzofurans ( 3 , 9 ) [72, 73], diphenyl-4-hydroxypiperidines ( 5 ) [74], spiro heterocycles ( 6 ) [75], benzimidazoles ( 7 ) [76] and biphenyls ( 8 ) [77]. N_2020 or compound 7 was dereplicated as an antimicrobial synthetic benzimidazole congener [76] and was a metabolite determined to be putatively specific against E .…”
Literature surveys, taxonomical differences, and bioassay results have been utilized in the discovery of new natural products to aid in Actinomycetes isolate-selection. However, no or less investigation have been done on establishing the differences in metabolomic profiles of the isolated microorganisms. The study aims to utilise bioassay- and metabolomics-guided tools that included dereplication study and multivariate analysis of the NMR and mass spectral data of microbial extracts to assist the selection of isolates for scaling-up the production of antimicrobial natural products. A total of 58 actinomycetes were isolated from different soil samples collected from Ihnasia City, Egypt and screened for their antimicrobial activities against indicator strains that included Bacillus subtilis, Escherichia coli, methicillin-resistant Staphylococcus aureus and Candida albicans. A number of 25 isolates were found to be active against B. subtilis and/or to at least one of the tested indicator strains. Principal component analyses showed chemical uniqueness for four outlying bioactive actinomycetes extracts. In addition, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and dereplication study led us to further select two outlying anti-MRSA active isolates MS.REE.13 and 22 for scale-up work. MS.REE.13 and 22 exhibited zones of inhibition at 19 and 13 mm against MRSA, respectively. A metabolomics-guided approach provided the steer to target the bioactive metabolites (P<0.01) present in a crude extract or fraction even at nanogram levels but it was a challenge that such low-yielding bioactive natural products would be feasible to isolate. Validated to occur only on the active side of OPLS-DA loadings plot, the isolated compounds exhibited medium to weak antibiotic activity with MIC values between 250 and 800 μM. Two new compounds, P_24306 (C10H13N2) and N_12799 (C18H32O3) with MICs of 795 and 432 μM, were afforded from the scale-up of MS.REE. 13 and 22, respectively.
“…The configuration of 11e could be determined by NOE analysis 13 of 4-acetoxypiperidine 15 , which was synthesized from 11e through transformations shown in Scheme . , 3 …”
[reaction: see text] We have developed an efficient copper-catalyzed allylation of carbonyl derivatives using allyl(2-pyridyl)silanes, in which the strong directing effect of the 2-pyridyl group was observed. A useful synthesis and allylation of substituted allyl(2-pyridyl)silanes is also described.
“…IR (KBr) max cm -1 : 3304 (NH), 1720 (С=O). 1 H NM R (400 M Hz, CHCl3, TM S) H ppm: 2.45 (2Н, d, J = 10.8 Hz, Н 23,25 ), 2.53 (2Н, br.s, Н 22,26 ), 2.92 (1Н, t, J = 12.9 Hz, NH), 3.01 (2Н, d, J = 10.8 Hz, Н 23,25 ), 3.68 (2Н, s, CH2Ph), 3.78-4.06 (8Н, m, OCH2CH2O), 4.53 (2Н, d.d, J = 12.9 and 2.9 Hz, Н 1,21 ), 6.81 (2Н, t, J = 7.4 Hz, Н 4,18 ), 6.88 (2Н, d, J = 8.1 Hz, Н 6,16 ), 7.11 (2Н, d.d, J = 7.3 and 1.4 Hz, Н 3,19 ), 7.20 (2Н, t.t, J = 8.1 and 1.4 Hz, Н 5,17 ).…”
Section: General Methods For Synthesis Of Azacrownophanes 3 Containin...mentioning
confidence: 99%
“…[1] For example, their oxime, thiosemicarbazone and tetrahydropyridine derivatives exhibit significant analgesic and local anesthetic activity as well as anti-fungal activity. [2][3][4] Transformation of piperidone into piperidine spirooxadiazole derivatives makes it as 7nicotinic receptor antagonists. [5] Therefore, the develop-ment of novel piperidone derivatives and study of their chemical and biological properties greatly attract the attention of scientists around the world.…”
Azacrownophanes containing fused piperidin-4-one fragment were successfully prepared through the modificatio n o f Petrenko-Kritschenko condensation or nucleophilic addition of the corresponding piperidone derivative with aryl a ldehyde followed by further cyclization. Acylation reaction of the synthesized azacrownophanes was performed u n d er reflux leading to the formation of target compounds with high yield. Acetic anhydride was used in excess as solvent and acylated agent. All new compounds were structurally confirmed by the physical-chemical methods including IR, 1 H NMR, MS and elemental analysis which contributed greatly to the library of crown ether class.
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