| 1. |
- Andersson, Maria, et al.
(författare)
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Synthesis and bioanalytical evaluation of morphine-3-O-sulfate and morphine-6-O-sulfate in human urine and plasma using LC-MS/MS
- 2012
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Ingår i: Journal of Separation Science. - : Wiley. - 1615-9306 .- 1615-9314. ; 35:3, s. 367-375
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to synthesize morphine-3-O-sulfate and morphine-6-O-sulfate for use as reference substances, and to determine the sulfate conjugates as possible heroin and morphine metabolites in plasma and urine by a validated LC-MS/MS method. Morphine-6-O-sulfate and morphine-3-O-sulfate were prepared as dihydrates from morphine hydrochloride, in overall yields of 41 and 39% with product purities of >99.5% and >98%, respectively. For bioanalysis, the chromatographic system consisted of a reversed-phase column and gradient elution. The tandem mass spectrometer was operated in the positive electrospray mode using selected reaction monitoring, of transition m/z 366.15 to 286.40. The measuring range was 5500?ng/mL for morphine-3-O-sulfate and 4.5454?ng/mL for morphine-6-O-sulfate in plasma. In urine, the measuring range was 505000?ng/mL for morphine-3-O-sulfate and 45.44544?ng/mL for morphine-6-O-sulfate. The intra-assay and total imprecision (coefficient of variation) was below 11% for both analytes in urine and plasma. Quantifiable levels of morphine-3-O-sulfate in authentic urine and plasma samples were found. Only one authentic urine sample contained a detectable level of morphine-6-O-sulfate, while no detectable morphine-6-O-sulfate was found in plasma samples.
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| 2. |
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| 3. |
- Harris, Kurt L., et al.
(författare)
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Ancestral Sequence Reconstruction of a Cytochrome P450 Family Involved in Chemical Defense Reveals the Functional Evolution of a Promiscuous, Xenobiotic-Metabolizing Enzyme in Vertebrates
- 2022
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Ingår i: Molecular biology and evolution. - : NLM (Medline). - 0737-4038 .- 1537-1719. ; 39:6
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Tidskriftsartikel (refereegranskat)abstract
- The cytochrome P450 family 1 enzymes (CYP1s) are a diverse family of hemoprotein monooxygenases, which metabolize many xenobiotics including numerous environmental carcinogens. However, their historical function and evolution remain largely unstudied. Here we investigate CYP1 evolution via the reconstruction and characterization of the vertebrate CYP1 ancestors. Younger ancestors and extant forms generally demonstrated higher activity toward typical CYP1 xenobiotic and steroid substrates than older ancestors, suggesting significant diversification away from the original CYP1 function. Caffeine metabolism appears to be a recently evolved trait of the CYP1A subfamily, observed in the mammalian CYP1A lineage, and may parallel the recent evolution of caffeine synthesis in multiple separate plant species. Likewise, the aryl hydrocarbon receptor agonist, 6-formylindolo[3,2-b]carbazole (FICZ) was metabolized to a greater extent by certain younger ancestors and extant forms, suggesting that activity toward FICZ increased in specific CYP1 evolutionary branches, a process that may have occurred in parallel to the exploitation of land where UV-exposure was higher than in aquatic environments. As observed with previous reconstructions of P450 enzymes, thermostability correlated with evolutionary age; the oldest ancestor was up to 35 °C more thermostable than the extant forms, with a 10T50 (temperature at which 50% of the hemoprotein remains intact after 10 min) of 71 °C. This robustness may have facilitated evolutionary diversification of the CYP1s by buffering the destabilizing effects of mutations that conferred novel functions, a phenomenon which may also be useful in exploiting the catalytic versatility of these ancestral enzymes for commercial application as biocatalysts.
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| 4. |
- Hasimbegovic, Vedran, et al.
(författare)
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The synthesis of some 3-acylindoles revisited
- 2007
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Ingår i: Journal of Heterocyclic Chemistry. - : Wiley. - 0022-152X .- 1943-5193. ; 44:5, s. 1213-1217
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Tidskriftsartikel (refereegranskat)abstract
- A study probing the scope of acylation of indoles with dicarboxylic acids in acetic anhydride has beenperformed, resulting in products incorporating 3-acylindole- or 1-acylindole motifs depending on thechoice of the acid reactant. Synthetically useful results were only obtained from reactions involvingmalonic acid or Meldrum’s acid. Correlations to previous studies have also been made and discussed.
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| 5. |
- Janosik, Tomasz, et al.
(författare)
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Chapter 5.2 Five-membered ring systems : Pyrroles and benzo derivatives
- 2005
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Ingår i: Progress in Heterocyclic Chemistry. - 0959-6380 .- 2542-680X. ; 16, s. 128-155
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- This chapter discusses the progress in synthesis and chemistry of pyrroles, indoles, and related fused ring systems. Several specialized reviews on the chemistry of indoles and pyrroles have appeared during the reporting period, providing more in-depth coverage. A comprehensive review on pyrrole natural products has appeared as well as a more limited one on the synthetic chemistry involving the pyrrole natural products roseophilin and prodigiosin is illustrated in this chapter. Likewise, the synthetic efforts in the field of the pyrrole-imidazole class of alkaloids have been covered. The isolation and synthesis of indole alkaloids containing a non-rearranged monoterpenoid unit is discussed in this chapter.
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| 6. |
- Janosik, Tomasz, et al.
(författare)
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Chemistry and Properties of Indolocarbazoles
- 2018
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Ingår i: Chemical Reviews. - : American Chemical Society (ACS). - 0009-2665 .- 1520-6890. ; 118:18, s. 9058-9128
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Tidskriftsartikel (refereegranskat)abstract
- The indolocarbazoles are an important class of nitrogen heterocycles which has evolved significantly in recent years, with numerous studies focusing on their diverse biological effects, or targeting new materials with potential applications in organic electronics. This review aims at providing a broad survey of the chemistry and properties of indolocarbazoles from an interdisciplinary point of view, with particular emphasis on practical synthetic aspects, as well as certain topics which have not been previously accounted for in detail, such as the occurrence, formation, biological activities, and metabolism of indolo[3,2-b]carbazoles. The literature of the past decade forms the basis of the text, which is further supplemented with older key references.
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| 7. |
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| 8. |
- Janosik, Tomasz, et al.
(författare)
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Derivatizing of Fast Pyrolysis Bio-Oil and Coprocessing in Fixed Bed Hydrotreater
- 2022
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Ingår i: Energy & Fuels. - : American Chemical Society. - 0887-0624 .- 1520-5029. ; 36:15, s. 8274-8287
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Tidskriftsartikel (refereegranskat)abstract
- In several countries forest-based biofuels are being developed and to some extent also deployed. Fast pyrolysis bio-oil produced from, for example, sawdust, has now been coprocessed in fluid catalytic cracking refinery units in a number of commercial trials. However, this application is limited to about 10% of the total feed, and coprocessing in conventional fixed bed hydrotreaters is necessary to reach the high potential with this feedstock. Feeding and upgrading of fast pyrolysis bio-oil in a fixed bed reactor configuration is still problematic due to the inherent bio-oil properties. Stabilization of reactive compounds in fast pyrolysis bio-oil and mild hydrotreatment in a separate refining unit prior to refinery integration has therefore been developed the past decade. Another approach, presented here, involves complete dewatering of fast pyrolysis bio-oil by azeotropic distillation using mesityl oxide as the solvent, followed by conversion of the abundant hydroxyl compounds via mixed anhydride esterification methodology using an external source of mixed carboxylic acids of different chain lengths originating from renewable tall oil fatty acids, providing a lipophilic feed component. Dewatering and derivatizing were carried out in reactors up to 50 dm3 with a mass ratio of fast pyrolysis bio-oil to tall oil fatty acid of 10:13. The produced lipophilic oils were miscible with a petroleum light gas oil fraction and exhibited superior stability even after accelerated aging at elevated temperature (80 °C). The derivatized oils were thus mixed with light gas oil, with a proportion of 30 wt % derivatized oil in final blends and hydrotreated continuously in pilot fixed bed reactors for 14 days at 4 operating conditions without plugging or excessive exotherms. The test conditions were varied; the reactor pressure was either 55 or 80 bar, temperature 380 or 400 °C, and liquid hourly space velocity either 1 or 2 h-1 during the hydrotreatment. Successful hydrodeoxygenation and desulfurization were accomplished, whereas an increasing nitrogen concentration could be observed in the liquid products with the particular catalyst and reaction conditions employed. The observed hydrogen consumption (15-20 g/kg feed) was compared with the stoichiometric consumption for direct deoxygenation and with typical consumptions for industrial hydrotreated vegetable oil processing. The measured biogenic carbon content in hydrotreated liquid products (26.7%) agreed extremely well with the calculated biogenic carbon content in the hydrotreating feed (26.6%) that consisted of the blend of derivatized oil and petroleum light gas oil. The overall results are very promising since simple unit operations can be used to produce derivatized fast pyrolysis bio-oils that do not need additional standalone hydrotreating units but can be coprocessed in existing ones
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| 9. |
- Janosik, Tomasz, et al.
(författare)
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Efficient sulfonation of 1-phenylsulfonyl-1H-pyrroles and 1-phenylsulfonyl-1H-indoles using chlorosulfonic acid in acetonitrile
- 2006
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 62:8, s. 1699-1707
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Tidskriftsartikel (refereegranskat)abstract
- The sulfonation of various 1-phenylsulfonyl-1H-pyrroles and 1-phenylsulfonyl-1H-indoles using chlorosulfonic acid in acetonitrile has been studied, leading to the development of a clean and operationally simple protocol allowing direct synthesis of the corresponding 1-phenylsulfonyl-1H-pyrrole-3-sulfonyl chlorides and 1-phenylsulfonyl-1H-indole-3-sulfonyl chlorides, respectively, both of which may be easily converted to various sulfonamide derivatives by treatment with nitrogen nucleophiles. Efficient and selective removal of the phenylsulfonyl- or tosyl groups in the sulfonamide series may be achieved under mild conditions.
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| 10. |
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