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1.
《Mutation Research Letters》1991,262(3):203-207
In order to elucidate the mechanisms of mutagenic activation of nitrobiphenyls by mammalian activation systems, 2,4,2′,4′-tetranitrobiphenyl was incubated with S9 and its mutagenic metabolites were separated by SiO2 and Al2O3 column chromatography. The most mutagenic diamino-dinitrobiphenyl was isolated from the reaction mixture of 2,4,2′ ,4′-tetranitrobiphenyl with S9 mix at 37°C for 48 h, and its mutability was 4646 revertants/50 ng in Salmonella typhimurium TA98 without S9 mix. The deamination product of this most mutagenic metabolite was identical to 2,4′-dinitrobiphenyl by gas chromatography-mass spectrometry. Therefore, the structure of the metabolite was determined as 2,4′-diamino-2′,4-dinitrobiphenyl by its chemical and physico-chemical properties. 相似文献
2.
Kilian Dill Sungho Hu Murugan Sutharchanadevi Alan R. Katritzky 《The protein journal》1988,7(4):341-348
The environment of the N-terminal amino groups of glycophorins AM and AN has been studied using13C-NMR spectroscopy and pyrylium salts as amino-blocking agents. The extent of amino blocking was monitored by13C-reductive methylation of the residual free amino groups. The pyrylium ions reacted with the N-terminal amino groups of the two glycophorins at almost identical rates, which is thought to indicate that the overriding steric bulk of the pyrylium salt may determine the rate of the reaction. The difference in the rates of modification of lysine residues of glycophorins AM and AN by the pyrylium ions did indicate that there may exist an environmental difference around the lysine residues between the two glycophorins. This environmental difference may result from solution aggregation of the glycophorin A molecules or from some differences in the pKa values of the five lysine residues found in glycophorins AM and AN. 相似文献
3.
Kilian Dill Sungho Hu Murugan Sutharchanadevi Alan R. Katritzky 《Journal of Protein Chemistry》1988,7(4):341-348
The environment of the N-terminal amino groups of glycophorins AM and AN has been studied using13C-NMR spectroscopy and pyrylium salts as amino-blocking agents. The extent of amino blocking was monitored by13C-reductive methylation of the residual free amino groups. The pyrylium ions reacted with the N-terminal amino groups of the two glycophorins at almost identical rates, which is thought to indicate that the overriding steric bulk of the pyrylium salt may determine the rate of the reaction. The difference in the rates of modification of lysine residues of glycophorins AM and AN by the pyrylium ions did indicate that there may exist an environmental difference around the lysine residues between the two glycophorins. This environmental difference may result from solution aggregation of the glycophorin A molecules or from some differences in the pKa values of the five lysine residues found in glycophorins AM and AN. 相似文献
4.
Anu Arya Divya Mathur Abhilash Tyagi Rajesh Kumar Vinod Kumar Carl E. Olsen 《Nucleosides, nucleotides & nucleic acids》2013,32(12):646-659
An efficient protocol has been developed for the synthesis of a small library of 3′-deoxy-3′-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reaction of 3′-azido-3′-deoxy-5-methyluridine with different alkynes under optimized condition in an overall yields of 76%–92%. Here, the azido precursor compound, i.e., 3′-azido-3′-deoxy-5-methyluridine was chemoenzymatically synthesized from D-xylose in good yield. Some of the alkynes used in cycloaddition reaction were synthesized by the reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using K2CO3in excellent yields. All synthesized compounds were unambiguously identified on the basis of their spectral (IR, 1H-, 13C NMR spectra, and high-resolution mass spectra) data analysis. 相似文献
5.
L-2,4-Diaminobutyric acid (Dab) reacts with K2PtCl4 yielding PtCl2(N,O-Dab), which rearranges to PtCl2(N,N-Dab). Reaction with L-ornithine and L-lysine yields the corresponding PtCl2(N,O-Orn) and PtCl2(N,O-Lys), respectively, whereas reaction with 4,5-diaminovaleric acid (Dav) yields PtCl2(N,N- Dav). 相似文献
6.
Acylation of quercetin with cinnamic acid catalyzed by Candida antarctica lipase B (CAL-B) or Pseudomonas cepacia lipase C (PCL-C) was investigated. Specifically, the effects of reaction duration, incubation temperature, and molar ratio of substrates on bioconversion yield, initial rate of reaction, and regioselectivity were investigated. Three new acylated quercetin analogues were produced: quercetin 4′-cinnamate (C24H16O8), quercetin 3′,4′-dicinnamate (C33H22O9), and quercetin 7,3′,4′-tricinnamate (C42H28O10). The effects of the lipase-catalyzed acylation conditions on the bioconversion yields varied across the conditions. The initial rate of reaction of acylation of quercetin with cinnamic acid catalyzed by CAL-B and PCL-C was similar. In the presence of CAL-B, acylation mainly took place at the C-4′-OH, generating mostly quercetin 4′-cinnamate; whereas with PCL-C, acylation mainly took place at both the 4′- and 3′-hydroxyls, generating quercetin 3′,4′-dicinnamate. Thin-layer-chromatography analysis showed that the three acylated quercetin analogues had higher lipophilicity when compared with quercetin. In silico investigation revealed that quercetin 4’-cinnamate and quercetin 3′,4′-dicinnamate are likely to be orally active pharmacological drugs. 相似文献
7.
Matthias Kinne Marzena Poraj-Kobielska Elisabet Aranda René Ullrich Kenneth E. Hammel Katrin Scheibner Martin Hofrichter 《Bioorganic & medicinal chemistry letters》2009,19(11):3085-3087
An extracellular peroxygenase of Agrocybe aegerita catalyzed the H2O2-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid) to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4′-hydroxydiclofenac (4′-OHD). The reactions proceeded regioselectively with high isomeric purity and gave the desired 5-OHP and 4′-OHD in yields up to 20% and 65%, respectively. 18O-labeling experiments showed that the phenolic hydroxyl groups in 5-OHP and 4′-OHD originated from H2O2, which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of drug metabolites. 相似文献
8.
Smriti Srivastava Sunil K. Singh Vivek K. Sharma Priyanka Mangla Carl E. Olsen 《Nucleosides, nucleotides & nucleic acids》2015,34(6):388-399
Three triazole-linked nonionic xylo-nucleoside dimers TL-t-TxL, TL-t-ABzxL and TL-t-CBzxL have been synthesized for the first time by Cu(I) catalyzed azide-alkyne [3 + 2] cycloaddition reaction (CuAAC) of 1-(3′-azido-3′-deoxy-2′-O,4′-C-methylene-β-D-ribo-furanosyl)thymine with different alkynes, i.e., 1-(5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylene-β-D-xylofuranosyl)thymine, 9-(5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylene-β-D-xylo-furanosyl)-N6-benzoyladenine and 1-(5′-deoxy-5′-C-ethynyl-2′-O,4′-C-methylene-β-D-xylofuranosyl)-N4-benzoylcytosine in 90%–92% yields. Among the two Cu(I) reagents, CuSO4.5H2O-sodium ascorbate in THF:tBuOH:H2O (1:1:1) and CuBr.SMe2 in THF used for cycloaddition (click) reaction, the former one was found to be better yielding than the latter one. 相似文献
9.
Norbert Bischofberger Mark D. Matteucci 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):859-862
Abstract We have synthesized polycyclic nucleoside derivatives by a novel, one pot procedure by reacting 4-0-TPS-pyrimidine nucleosides with aromatic diamines. The reaction is limited in scope but provides easy access to certain previously unknown heterocyclic ring systems.2 4-0-Triisopro- pylphenylsulfonyl-pyrimidine nucleosides were reacted with aromatic diamines leading to fused, polycyclic ring systems: o-phenylenediamine yielded the pyrimido[1,6-a]benzimidazole, 2.3- diaminonaphthalene gave the naphth[2′,3′:4,5]imidam [1.2-flpyrimidine and 1.8-diaminonaph- thalene led to the pyrimido[l,6-a]perimidine ring system. The reaction is unique because two connected nucleophilic centers react with the pyrimidine nucleoside to form an extended ring system. However, reactions of pyrimidine nucleosides with electrophiles are well known. E.g., reaction of cytidine and adenosine with bromoacetaldehyde yields ethenocytidine and ethenoadenosine) and on reaction of cytidine with 1′-methylthiaminium salts dipyrimido[1,6-a:4′,5′-d]pyrimidine derivatives are obtained.4 Other polycyclic bases have been made from cytidine and adenosine by photochemical reactions5. 相似文献
10.
Kenji Kanaori Kayo Yokoyama Kunihiko Tajima Nobuko Yamamoto Tadashi Okamoto Keisuke Makino 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):603-611
Abstract Interaction of 2-methyl-4,6-bis-(4-N,N-dimethylaminophenyl) pyrylium salt (P2) with [d(CGACGTCG)]2 was investigated by H NMR spectroscopy. The aromatic signals of P2 and the oligomer were shifted to the upfield by forming the complex, and intermolecular NOEs were also observed between P2 and the terminal CpG base steps but not between P2 and the central CpG. These results indicate that P2 binds to the weakly stacking CpG steps in an intercalation manner. 相似文献
11.
Effects of Selected Herbicides on Plant Protoplasts 总被引:1,自引:0,他引:1
Plant protoplasts were released from immature tomato fruits by incubation with a 20% solution of polygalacturonase (Pectinol R-10, Rhom & Haas) dissolved in 0.1 M KCl + 0.1 M MgCl2. In this salt solution the protoplasts remained stabilized for up to 8 h and were used as a source of exposed plasma membrane. Gross responses of protoplasts to selected chemicals and herbicides were recorded photomicroscopically. Paraquat (1,1′-dimethyl-4,4′-bipyridinium ion) treatments resulted in a characteristic response which was different from that of general denaturants (trichloroacetic acid, ethanol, and detergents) and of osmotic shock. Initial phases of the paraquat response were characterized by a segregation of the cytoplasm into isolated areas on the inner membrane surface. The final phase was a rupture of the plasma membrane and collapse of the cell. The herbicides, 2,4′-dinitro-4-trifluoromethyl-diphenylether (preforan); 1,1-dimethyl-3-(α,α,α-trifluoro-m-tolyl)urea (fluometuron); 3-(3-chloro-4-bromophenyl)-1-methoxy-1-methylurea (chlorbromuron); and α,α,α-trifluoro-2,6-dinitro-N-N-dipropyl-p-toluidine (trifluralin) produced no apparent structural effect on the protoplasts. 相似文献
12.
Alkaline degradation of Aurasperone A, C32H26O10, gave a binaphthyl (IIa), m.p. 255°C and acetone. (IIa) afforded a tetraacetate (IIb), C32H30O12 m.p. 219°C and a tetramethyl ether (IId), C28H30O8, m.p. 188°C. These facts along with the NMR spectra of aurasperone A and (IIb) confirm that aurasperone A is a dimeric 2-methyl-5-hydroxy-6,8-dimethoxy-4H-naphtho[2,3-b]pyran-4-one with asymmetric C-C linkage (7-10′ or 9-10′). The ether (IId) is not identical with 1,1′ ,3,3′ ?6,6′ ,8,8′-octamethoxy-4,4′-binaphthyl. Thus, it follows that (IId) is a 2,4′-binaphthyl and hence aurasperone A is 2,2′-dimethyl-5,5′- dihydroxy-6,6′,8,8′-tetrahydroxy-7,10′-bi[4H-naphtho[2,3-b]pyran-4-one] (I). 相似文献
13.
Naoki Uchiyama Toshihiko Ogata Natsuhisa Oka Takeshi Wada 《Nucleosides, nucleotides & nucleic acids》2013,32(6):446-456
Arylmethyl groups such as benzyl, p-methoxybenzyl, and 1-pyrenylmethyl groups were introduced to the 2′-O-position of nucleosides by reductive etherification. Combining corresponding aromatic aldehydes with 2′-O-trimethylsilylnucleoside derivatives in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) resulted in moderate to good yields of the 2′-O-arylmethyluridine derivatives, whereas the corresponding cytidine and adenosine derivatives were obtained in low yields. The reaction of ribonucleosides with aliphatic aldehydes did not proceed smoothly. Anomerization of the uridine derivatives by TMSOTf was observed in CH2Cl2, toluene, and CH3CN, but was completely suppressed when the reactions were conducted in 1,4-dioxane. 相似文献
14.
Shin-Ichi Ayabe Takafumi Yoshikawa Miyuki Kobayashi Tsutomu Furuya 《Phytochemistry》1980,19(11):2331-2336
In order to clarify the O-methylation step in the biosynthesis of a retrochalcone, echinatin(4,4′-dihydroxy-2-methoxychalcone), methyl transfer from S-adenosyl-l-methionine (SAM) to licodione (1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-1,3-propanedione) in the cell-free extract of the cultured cells of Glycyrrhiza echinata was examined. Time course of methyl transferring activity during culture cycle in 4 strains was correlated to echinatin content. The enzyme catalysing this reaction, licodione O-methyltransferase (LMT), was purified 135-fold. Substrate specificity studies implied that the hydroxy group ortho to the C3 linkage in licodione was methylated in this reaction. O-Methyl-licodiones were synthesized for comparison and the sole product of LMT-catalysed reaction was identified as 2′-O-methyl-licodione. A possible scheme for the last steps of echinatin biosynthesis is proposed. 相似文献
15.
《Phytochemistry》1987,26(12):3233-3234
A crude enzyme preparation obtained from cell suspension culture of Catharanthus roseus converted 3′,4′-anhydrovinblastine to vinblastine, an anticancer agent. NADH and MnCl2 in the reaction mixture enhanced vinblastine yields. 相似文献
16.
Hydroxyl Radical-Mediated Oxidation of Serotonin: Potential Insights into the Neurotoxicity of Methamphetamine 总被引:1,自引:1,他引:0
Monika Z. Wrona Zhaoliang Yang Michelle McAdams Susan O'Connor-Coates Glenn Dryhurst 《Journal of neurochemistry》1995,64(3):1390-1400
Abstract: When incubated with a hydroxyl radical (HO?)-generating system (ascorbic acid/Fe2+-EDTA/O2/H2O2), 5-hydroxytryptamine (5-HT; serotonin) is rapidly oxidized initially to a mixture of 2,5-, 4,5-, and 5,6-dihydroxytryptamine (DHT). The major reaction product is 2,5-DHT, which at physiological pH exists as its keto tautomer, 5-hydroxy-3-ethylamino-2-oxindole (5-HEO). Rapid autoxidation of 4,5-DHT gives tryptamine-4,5-dione (T-4,5-D), which reacts with the C(3)-centered carbanion of 5-HEO to give 3,3′-bis(2-aminoethyl)-5-hydroxy-[3,7′-bi-1H-indole]-2,4′,5′-3H-trione (7). The latter slowly cyclizes to 3′-(2-aminoethyl)-1′,6′,7′,8′-tetrahydro-5-hydroxyspiro[3H-indole-3,9′-[9H]pyrrolo[2,3-f]quinoline]-2,4′,5′(1H)- trione (9). A minor amount of T-4,5-D dimerizes to give 7,7′-bi-(5-hydroxytryptamine-4-one) (7,7′-D). In the presence of GSH, the reaction of T-4,5-D with 5-HEO is diverted and, in the presence of sufficient concentrations of this tripeptide, completely blocked. This is because GSH preferentially reacts with T-4,5-D to give 7-S-glutathionyltryptamine-4,5-dione (11). The results of this investigation suggest that 5,6-DHT, 5-HEO, 7, and 9 are products unique to the HO?-mediated oxidation of 5-HT. Thus, the observation of other investigators that 5,6-DHT is formed in the brains of rats following a large dose of methamphetamine (MA) suggests that this drug might evoke HO? formation. However, the present in vitro study indicates that 5,6-DHT is a rather minor, unstable product of the HO?-mediated oxidation of 5-HT and suggests that detection of 5-HEO, 7/9, and 11 in rat brain following MA administration could provide additional support for HO? formation. Furthermore, one or more of the intermediates and major products of oxidation of 5-HT by HO? might, in addition to 5,6-DHT, contribute to the MA-induced degeneration of serotonergic neurons. 相似文献
17.
Raju Ranjith Kumar Subbu Perumal S.C. Manju Pritesh Bhatt Perumal Yogeeswari Dharmarajan Sriram 《Bioorganic & medicinal chemistry letters》2009,19(13):3461-3465
The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and α-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) using agar dilution method. Two compounds, 4-(2,4-dichlorophenyl)-5-phenylpyrrolo(spiro[2.2″]acenaphthene-1″-one)spiro[3.2′]-6′-(2,4-dichlorophenylmethylidene)cyclohexanone (4i) and spiro[5.2″]acenaphthene-1″-onespiro[6.2′]-6′-(2,4-dichlorophenylmethylidene)cyclohexanone-7-(2,4-dichlorophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole (5i) display maximum activity in vitro with a MIC value of 0.40 μg/mL against MTB and were 4 and 15.6 times more potent than ethambutol and pyrazinamide, respectively. 相似文献
18.
Abstract— Separation of 2′-adenosine monophosphate from 2′,3′-cyclic adenosine monophosphate by coprecipitation with a number of salt mixtures was examined and found to be most successful with Na2CO3/CdCl2 and Na2CO3/ZnSO4. A simple and rapid assay for 2′,3′-cyclic nucleotide 3′-phosphohydrolase using coprecipitation with Na2CO3/CdCl2 is described. 相似文献
19.
R. K. Singh S. Ohuchi T. Wada T. Hata# 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):123-130
Abstract 5′-Chloro-5′-deoxy-N,3′-O-dibenzoylthymidine (3a), 5′-chloro-5′-deoxy-N4, 3′-O-dibenzoyldeoxycytidine(3b), 5′-chloro-5′-deoxy-N6,3′-O-dibenzoyldeoxyadenosine(3c), N-benzoyl-1-(3-chloro-2,3-dideoxy-5-O-trityl-ß-D-xylofuranosyl)thymine (5a) and N6-benzoyl-9-(3-chloro-2,3-dideoxy-5-O-trityl-ß-D-xylofuranosyl)adenine (5b) have been synthesized in very high yields using a new efficient reagent, tris(2,4,6-tribrom-ophenoxy)dichlorophosphorane (BDCP). The reaction time was greatly reduced to 5–8 min. NOE data suggested an inversion of configuration at C3-position and thus an SN2 mechanism has been proposed for the chlorination reaction. 相似文献
20.
《Nucleosides, nucleotides & nucleic acids》2013,32(12):2121-2132
Abstract A group of unnatural 1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorobenzenes possessing a 5-I or 5-CF3 substituent, that were originally designed as thymidine mimics, were coupled via their 5′-OH group to a cyclosaligenyl (cycloSal) ring system having a variety of C-3 substituents (Me, OMe, H). The 5′-O-cycloSal-pronucleotide concept was designed to effect a thymidine kinase-bypass, thereby providing a method for the intracellular delivery and generation of the 5′-O-monophosphate for nucleosides that are poorly phosphorylated. The 5′-O-cycloSal pronucleotide phosphotriesters synthesized in this study were obtained as a 1:1 mixture of two diastereomers that differ in configuration (S P or R P) at the asymmetric phosphorous center. The (S P)- and (R P)-diastereomers for the 5′-O-3-methylcycloSal- and 5′-O-3-methoxycycloSal derivatives of 1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene were separated by silica gel flash column chromatography. This class of cycloSal pronucleotide compounds generally exhibited weak cytotoxic activities in a MTT assay (CC50 values in the 10?3 to 10?4 M range), against a number of cancer cell lines (143B, 143B-LTK, EMT-6, Hela, 293), except for cyclosaligenyl-5′-O-[1′-(2,4-difluoro-5-iodophenyl)-2′-deoxy-β-D-ribofuranosyl]phosphate that was more potent (CC50 values in the 10?5 to 10?6 M range), than the reference drug 5-iodo-2′-deoxyuridine (IUDR) which showed CC50 values in the 10?3 to 10?5 M range. 相似文献