Skatole Research Articles

Interrupted Intramolecular Hydroaminomethylation of N-Protected-2-vinyl Anilines: Novel Access to 3-Substitued Indoles or Indoline-2-ols.

A new synthetic alternative to the synthesis of 3-methyl indoles and 3-methyl indoline-2-ols with an excellent atomic economy is presented in this study. It is demonstrated that the intramolecular interrupted hydroaminomethylation (HAM) reaction is a powerful tool for the formation of these compounds, which exhibit wide-ranging biological activity. Several N-Protected-2-vinyl anilines were synthesized and involved in the reaction producing the corresponding 3-methylindole or 3-methyl indoline-2-ol depending on the nature of the N-protecting groups.

THE PROCESSING OF WHITE PEPPER BY FERMENTATION THROUGH SOAKING TIME AND CONCENTRATION OF Bacillus Subtilis INOCULUM ON QUALITY AND OFF FLAVOUR CONTENT

<p>The processing of white pepper is still done traditionally, namely by soaking in unclean water that it can cause product contamination by unwanted microorganisms. The present work was to find out the effect of white pepper processing by fermentation using Bacillus subtilis inoculum through the length of soaking time and concentration of the inoculum on the quality and off-flavor compounds. The research method was carried out in several stages, namely the preparation of B. subtilis inoculum, preparation of raw materials, fermentation of pepper, decortication, drying using an oven at 50 ° C, analysis of quality and of off flavor compounds. The results showed that the soaking time has a significant effect on the content of light pepper, piperine, essential oil, and the color of the pepper. The concentration of B. subtilis inoculum has a significant effect on the quality of piperine, essential oil, and pepper color. The interaction between the soaking time and B. subtilis concentration has significantly affected the quality of piperine and essential oil levels. The soaking time of pepper for 7 days and the varying concentration of B. subtilis inoculums produced better quality pepper compared to the length of soaking for 5 days. White pepper with the lowest TPC value was from soaking for 5 days with B. subtilis inoculum concentration of 20% was 1.86x103 CFU / g. From the analysis of off-flavor compounds in the 5-days fermentation were identified 4 off flavor compounds, i.e., propanoic, butanoic, hexanoic acids and piperonal, while the 7-days with the same compound and the addition of 2 other compounds, namely p-cresol and 2 H methyl indole.</p>

Microwave-Assisted Multi-Component Green Synthesis of Benzo[α]furo[2, 3-c]phenazine Derivatives via a Magnetically-Separable Fe3O4@rGO@ZnO-HPA Nanocatalyst under Solvent-Free Conditions

A novel and efficient method for the synthesis of benzo[α]furo[2, 3-c]phenazine derivatives by the reaction of benzo[a]phenazin-5-ol, Arylglyoxals, and methyl indole in the present Fe3O4@rGO@ZnO-HPA magnetic core-shell nanoparticles (MCNPs) under microwave reaction is reported. The catalyst was characterized by FT-IR, TEM, FESEM, XRD, AFM, hot-filtration, and VSM techniques. The advantages of a method are High yields, short reaction time (10–15 min), operational simplicity, absence of any tedious workup or purification, and avoidance of hazardous or toxic reagents/solvents are the salient features of this eco-friendly methodology.

Synthesis of 3,3′- Di-indolylmethanes under mild conditions by Microwave Irradiation Mediated Reactions of Indoles with C, N-Diaryl nitrones

3,3′-Di-indolylmethane derivatives are important biologically active compounds possessing anti-cancer properties. Hence, development of synthetic routes to these are of great interest to organic chemists. In the present communication we report a high-yield method using mild reaction conditions and short reaction times for the synthesis of 3,3′-di-indolylmethane derivatives. The method involved reactions of indole and substituted indoles with C,N-disubstituted nitrones in the presence of acid catalysts, with the utilisation of microwave irradiation techniques. Reactions of indole, 2-methyl indole and 2-phenyl indole were performed with ten different C,N-diaryl- and C-aryl-N-methyl- nitrones in dichloromethane solution in the absence and presence of acid catalysts, viz. ytterbium triflate, p-toluene sulphonic acid and Montmorillonite clay K-10. Reaction times varied between 2 to 18 minutes. In general, yields of the catalysed reactions were above 75%. The products were characterised spectroscopically, including two-dimensional NMR studies. The microwave irradiation technique enhanced reaction rates by a significant amount. Ytterbium triflate proved to be the best catalyst, giving clean reactions, without formation of by-products, in high yields. The structure and conformation of 3,3′-di-indolyl-phenylmethane were computed. GRAPHICAL ABSTRACT: We report a high-yield method using mild reaction conditions and short reaction times for the synthesis of 3,3′-di-indolylmethane derivatives, involving reactions of indole and substituted indoles with C, N-disubstituted nitrones in the presence of acid catalysts using microwave irradiation.

Endocrine Fertility Parameters-Genomic Background and their Genetic Relationship to Boar Taint in German Landrace and Large White.

Simple SummaryBreeding against boar taint compounds androstenone and skatole can be an efficient alternative for surgical castration of young piglets during their first week of life to avoid boar taint. Physiological links of androstenone to steroid hormones in the synthesis pathway are documented and they have to be analyzed for their genetic effects on reproduction and fertility. While using boar taint and hormone data from Landrace and Large White pigs (commercial nucleus populations and herd book populations), the effects of breeding against androstenone on fertility were evaluated. Moreover, the genetic foundation of the chosen hormones’ testosterone, 17β-estradiol, luteinizing hormone, follicle-stimulating hormone, and progesterone was analyzed and then checked for possible pleiotropic effects with boar taint compounds. The results showed consistent unfavorable side effects of breeding against androstenone on testosterone and 17β-estradiol in both breeds. The other hormones showed contrary results regarding unfavorable relationships between boar taint and endocrine fertility parameters. The genetic foundation showed a high potential of breeding against boar taint but the impact on fertility potential should be supervised.The surgical castration of young male piglets without anesthesia is no longer allowed in Germany from 2021. One alternative is breeding against boar taint, but shared synthesis pathways of androstenone (AND) and several endocrine fertility parameters (EFP) indicate a risk of decreasing fertility. The objective of this study was to investigate the genetic background between AND, skatole (SKA), and six EFP in purebred Landrace (LR) and Large White (LW) populations. The animals were clustered according to their genetic relatedness because of their different origins. Estimated heritabilities (h2) of AND and SKA ranged between 0.52 and 0.34 in LR and LW. For EFP, h2 differed between the breeds except for follicle-stimulating hormone (FSH) (h2: 0.28–0.37). Both of the breeds showed unfavorable relationships between AND and testosterone, 17-β estradiol, and FSH. The genetic relationships (rg) between SKA and EFP differed between the breeds. A genome-wide association analysis revealed 48 significant associations and confirmed a region for SKA on Sus Scrofa chromosome (SSC) 14. For EFP, the results differed between the clusters. In conclusion, rg partly confirmed physiologically expected antagonisms between AND and EFP. Particular attention should be spent on fertility traits that are based on EFP when breeding against boar taint to balance the genetic progress in both of the trait complexes.

Synthesis of 3-Methyl Indoles via Catellani Reaction

Synthesis of 3-Methyl Indoles via Catellani Reaction

P20 - Dual effects of methylated indoles on CYP1A1 in human hepatocytes

P20 - Dual effects of methylated indoles on CYP1A1 in human hepatocytes

Gas Chromatography Mass Spectrometry (GC-MS) Quantification of Metabolites in Stool Using 13C Labelled Compounds.

It has become increasingly important to qualitatively and quantitatively assess the volatile metabolites in a range of bodily fluids for use in monitoring health. There has been relatively little work on the quantitative analysis of compounds, particularly with respect to the effects of ethnicity or geographic location. A novel method for the quantification of compounds in stool using 13C labelled compounds as internal standards is presented. Using thermal desorption gas chromatography mass spectrometry, stool samples from 38 healthy volunteers were analysed. The 13C labelled compounds, acetone, ethyl butanoate, ethanoic acid, butanoic acid, 3-methylbutanoic acid, and indole, were added as internal standards. This process mimics the solubility characteristics of the compounds and thus the method was able to quantify the compounds within the solid stool. In total, 15 compounds were quantified: Dimethyl sulphide (26–25,626 ng/g), acetone (442–3006 ng/g), ethyl butanoate (39–2468 ng/g), ethyl 2-methylbutanoate (0.3–180 ng/g), dimethyl disulphide (35–1303 ng/g), 1-octen-3-one (12 ng/g), dimethyl trisulphide (10–410 ng/g), 1-octen-3-ol (0.4–58 ng/g), ethanoic acid (672–12,963 ng/g), butanoic acid (2493–11,553 ng/g), 3-methylbutanoic acid (64–8262 ng/g), pentanoic acid (88–21,886 ng/g), indole (290–5477 ng/g), and 3-methyl indole (37–3483 ng/g). Moreover, by altering the pH of the stool to pH 13 in conjunction with the addition of 13C trimethylamine, the method was successful in detecting and quantifying trimethylamine for the first time in stool samples (range 40–5312 ng/g). Statistical analysis revealed that samples from U.K. origin had five significantly different compounds (ethyl butanoate, 1-octen-3-ol, ethanoic acid, butanoic acid, pentanoic acid, and indole) from those of South American origin. However, there were no significant differences between vegetarian and omnivore samples. These findings are supported by pre-existing literature evidence. Moreover, we have tentatively identified 12 compounds previously not reported as having been found in stool.

Hydrothermal reaction of tryptophan over Ni-based bimetallic catalysts

The major products from hydrothermal reactions of tryptophan at 350 and 400 °C in the absence of catalyst were indole and methyl indoles, indicating simultaneous deoxygenation and deamination. In the presence of carbon-supported Ni and NiM catalysts (M = Ru, Cu, Pd, Pt) primary aromatic amines also appeared, via cleavage of the heterocyclic ring of the indoles. Ni and NiCu catalysts have the lowest selectivity for the formation of this family of compounds, while NiRu had the highest selectivity. Catalysts containing noble metals also produced monosubstituted alkylaromatics, due to the deamination of the aromatic amines, with the NiPt catalyst providing the highest molar yield (∼7%). We propose catalytic and non-catalytic hydrothermal reaction pathways for tryptophan based on the observed product distributions. The bimetallic particles were smaller than the pure Ni particles and the surfaces of NiRu and NiPd particles were enriched in Ni, relative to the nominal bulk composition.

Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies

A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer.Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use.In the present study aromatase inhibiting potential of 2-methyl indole hydrazones are investigated, and compared with melatonin, by two in vitro models; a cell-free assay using a fluorescence substrate and a cell-based assay where cell proliferation was determined in ER + human breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone. Aromatase inhibitory effect is also explored by molecular modelling studies.In biological activity assays monochloro substituted indole hydrazones were found to have stronger aromatase inhibitory activity among all tested derivatives and were more active than melatonin. This finding is further confirmed by molecular modelling.These results may be useful in the design and synthesis of novel melatonin analogues with higher inhibitory potency against aromatase.

Sorptive process and breakthrough behavior of odorous volatile compounds on inert surfaces

The use of glass impinger is an important device for sampling and handling when measuring volatile organic compounds (SVOCs). Thus, it is important to check for possible analyte losses to the inner glass surface when carrying out sample analysis with the aid of impinger system. In this research, we evaluated the sorptive loss patterns of vapor-phase semi-volatile organic compounds [SVOCs (n = 10): acetic acid (ACA), propionic acid (PPA), i-butyric acid (IBA), n-butyric acid (BTA), i-valeric acid (IVA), n-valeric acid (VLA), phenol (PhAl), p-cresol (p-C), indole (ID), and skatole (SK)] on inert surfaces of an impinger in reference to sampling bags. The gaseous standard of these SVOCs (48–406 ppb) in polyester aluminum (PEA) bags was passed through an empty impinger in 1 L steps. The exiting SVOCs were collected on three-bed sorbent tubes for subsequent analysis by thermal desorption-gas chromatography-mass spectroscopy (TD-GC-MS). Impinger wall sorption capacities ranged from 2.0 to 21.0 ng cm−2. The 10% breakthrough adsorption capacities on the impinger wall for acids, phenols, and indoles ranged from 1.21 ± 0.15 to 5.39 ± 0.79, 0.92 ± 0.12 to 13.4 ± 2.25, and 4.47 ± 0.42 to 5.23 ± 0.35 ng cm−2, respectively. The observed sorptive patterns suggest that the sorptive losses of the volatile fatty acids, phenols, and indoles can occur very effectively at low ppb levels onto a glass surface.

Whole-molecule disorder in the crystal structures of 7-chloro and 7-methyl indole

Whole-molecule disorder in the crystal structures of 7-chloro and 7-methyl indole

On farm intervention studies on reduction of boar taint prevalence: Feeding strategies, presence of gilts and time in lairage

One of the challenges in the production of entire male pigs is the occurrence of boar taint. We separately tested the effect of 3 management strategies to reduce boar taint on respectively 2, 3, and 6 Flemish pig farms: 1) adapted feeding strategies, 2) presence of gilts in the compartment, and 3) varying lairage duration at the slaughterhouse.A commercialized feed concept resulted in a significant reduction of olfactory boar taint prevalence when fed for 2 weeks (T2W) compared to control (T-CON) (P = 0.030). For T2W and when fed for 3 weeks (T3W), androstenone (AND) (P = 0.002 for T2W, P = 0.029 for T3W) and skatole (SKA) (P < 0.001 for T2W and T3W) were significantly reduced compared to T-CON. Olfactory boar taint prevalence was significantly reduced when feeding 5% dried chicory roots (FI5%) (P = 0.032), but not for 3% dried chicory roots (FI3%) (P = 0.958). SKA concentration was significantly lower when feeding FI5% (P < 0.001) and when feeding FI3% (P = 0.034). Rearing entire male pigs separately from gilts and increasing lairage duration from <1 h to >3 h did not significantly affect boar taint.

1,3-Iodo-amination of 2-methyl indoles via Csp2-Csp3 dual functionalization with iodine reagent.

A 1,3-iodo-amination with iodine reagent that involved the Csp2-Csp3 dual functionalization of 2-methyl indoles was developed to provide 2-aminomethyl-3-iodo-indole derivatives. The iodo-amination proceeded via a 1,4-transfer of an imide group through the formation of an indolyl(phenyl)iodonium imide using PhI(OAc)2, followed by an iodination using DIH or a double iodination of indole using excess DIH.

Differentiation of methylated indole ring regioisomers of JWH-007: GC–MS and GC–IR studies

The five regioisomeric methylated indole ring analogues of JWH-018 can be prepared directly from a common set of precursor materials. These five isomers include 2-methyl-1-n-pentyl-3-(1-naphthoyl)-indole (JWH-007) and its four regioisomeric analogues, 4-, 5-, 6- and 7-methyl substituted indoles. The EI-MS spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. The characteristic [M−17]+ fragment ion at m/z 338 resulting from the loss of OH group is significant in the mass spectra of all the studied compounds except Compound 2 (JWH-007) which has two significant fragment ions at m/z 340 and m/z 270. Cations at m/z 298, 284, 228 and 200 result from fragmentation of the naphthoyl and/or n-pentyl groups. GC separations on a trifluoropropylmethyl polysiloxane (Rtx-200) provided excellent resolution of these compounds. The elution order appears to be related to the degree of crowding of indole ring substituents. The vapor phase infrared spectra in the range of 1700–700 cm−1 showed unique and characteristic absorption patterns for each of the five regioisomeric compounds which allowed for discrimination among the isomers in this set of cannabinoid compounds.

Influence of C1375 Liquid Deodorant to the Microbial Coagulation and Volatile Contents of Fresh Latex

In order to alleviate the smelly odor of microbial coagula, C1375 liquid deodorant was mixed with microbial coagulation liquid in the fresh latex before coagulation began. Then the effect of strain C1375 addition on fresh latex microbial coagulation and its volatile component content was investigated. Slight influence on fresh latex microbial coagulation was observed from the C1375 deodorant addition. Compared to the original microbial coagula, the C1375 added coagula contained more compounds of alkyl alkene while less benzene series. Besides C1375 liquid deodorant can effectively reduce the content of 3-methyl indole, phenol, L- limonene and other volatile substances, which leads to efficient reduction of the wet microbial coagula smell.

A copper-catalyzed tandem reaction for the construction of coumarin fused 9H-pyrrolo[1,2-a]indoles.

An efficient copper-catalyzed Friedel-Crafts alkylation/cyclization/isomerization sequence of 3-arylcarbonyl coumarins and 3-methyl indole was developed to afford a wide range of functionalized coumarin fused 9H-pyrrolo[1,2-a]indoles, which feature a 6-6-5-5-6 pentacyclic core, in 34-99% yields. Moreover, gram-scale experiment and chemical transformations were conducted to demonstrate the synthetic value of this protocol.

Olfactory evaluation of boar taint: effect of factors measured at slaughter and link with boar taint compounds

There is a commitment by the European pig sector to ban surgical castration of male piglets in the European Union in 2018. One alternative to castration is to raise entire male pigs, with an increased risk of boar taint. A field study was performed to: (1) evaluate inter- and intra-farm variation in boar taint prevalence, (2) investigate factors measured at slaughter influencing boar taint and (3) evaluate the relationship between sensorial scoring by a trained panel and the concentration of boar taint components. From 34 farms, neck fat samples were collected from all entire male pigs in at least two slaughter batches per farm (78 batches; 9167 animals). In addition to olfactory boar taint analysis, data were also collected on fresh skin lesions (score 0 to 3) at the slaughter line, slaughter weight, lean meat percentage, duration of transport, time spent in lairage, total delivery duration, day length, shortening of days and outdoor mean temperature. Using the hot iron method, neck fat samples were scored (eight-point scale) for boar taint. Average boar taint prevalence (score ≥3) was 5.6±2.5% and the mean difference between the maximum and minimum prevalence per farm was 4.3±3.2%. Androstenone (AND), skatole (SKA) and indole concentrations were measured for a subset (n=254) of the samples. According to binomial univariate mixed models, entire male pigs with a higher skin lesion score had higher odds of having boar taint (P=0.031), as did fatter entire male pigs (P<0.001). In the binomial multivariate mixed model lean meat percentage (P<0.001) and outdoor mean temperature (P=0.005) remained as only significant factors. Based on our results, we can conclude that these statistically significant at least partially influence the prevalence of boar taint. According to the binomial univariate mixed models SKA concentration in liquid fat seems a better predictor for boar taint than AND. There were no significant synergetic effects between boar taint compounds.

Further Insight into the Mechanism of the Novel Multicomponent Reactions Involving Isoquinoline and Dimethyl Acetylenedicarboxylate in the Presence of 3-Methylindole: Theoretical and Experimental Approach

The kinetics of the reactions among isoquinoline, dimethyl acetylenedicarboxylate, and 3-methyl indole (as NH-acid) was studied using UV spectrophotometry. The overall rate constant (kov) was evaluated from the slope of the plot of kobs versus reactant concentration. A large deal of useful information was obtained from the study of the effects of solvent, temperature, and reactants and concentration on the reaction rates. Based on experimental data and theoretical concepts, the reaction's first step (k1) was recognized as the rate-determining step. Theoretical studies were performed to evaluate potential energy surfaces of all components participated in the reaction mechanism. Furthermore, the proposed mechanism was confirmed by the obtained results. The probable reaction path and product configuration were suggested based upon the theoretical results.

Design, synthesis and investigation of dual benefits of 2-methyl indole derivatives in hormone-dependent breast cancer: Aromatase inhibitory and antioxidant activity

Design, synthesis and investigation of dual benefits of 2-methyl indole derivatives in hormone-dependent breast cancer: Aromatase inhibitory and antioxidant activity