共查询到20条相似文献,搜索用时 31 毫秒
1.
Guan W Ban L Cai L Li L Chen W Liu X Mrksich M Wang PG 《Bioorganic & medicinal chemistry letters》2011,21(17):5025-5028
A library of 11 UDP-N-acetylglucosamine analogs were rapidly screened for their activities as donors for the Neisseriameningitidis β1,3-N-acetylglucosaminyltransferase (LgtA) by direct on-chip reaction and detection with SAMDI-TOF mass spectrometry. Six of the analogs were active in this assay and were analyzed by SAMDI to characterize the kinetics toward LgtA. The analysis revealed that substitutions on C-2, C-4, and C-6 affect the activity of the donors, with bulky groups at these positions decreasing affinity of the donors for the enzyme, and also revealed that activity is strongly affected by the stereochemistry at C-3, but not C-4, of the donor. The study is also significant because it demonstrates that SAMDI can be used to both profile glycosyltransferase activities and to provide a quantitative assessment of enzyme activity. 相似文献
2.
Kaidong Zhang 《Carbohydrate research》2009,344(5):576-594
We describe the synthesis of two glucose-templated proline-lysine chimeras (GlcTProLysCs) that differ in the stereochemistry of the hydroxymethyl substituent at the C-5′ position of the pyrrolidine ring. The key synthetic steps involve C-glycosylation of an exocyclic glucose-based epoxide with allyltributylstannane, which affords functionalized C-ketosides containing an α-hydroxy ester moiety; introduction of an amino group at C-2 through stereoselective reductive amination; and regioselective installation of the azide group at C-6 on the glucose scaffold. Incorporation of these chimeras into the model peptides Ac-GlcTProLysC-NHMe and Ac-GlcTProLysC-OMe demonstrates that the stereochemistry of the hydroxymethyl substituent at the C-5′ position has a profound effect on the equilibrium constant of prolyl amide cis/trans isomerization. The equilibrium constant Kc/t for the peptide mimic Ac-GlcTProLysC-NHMe with C-5′(R) stereochemistry was determined to be 3.03 ± 0.04, while the Kt/c for the C-5′(S) diastereoisomer was 0.56 ± 0.04 in D2O. Temperature coefficient experiments indicate that the origin of these effects is derived from two critical hydrogen bonds involving the C-5′ hydroxymethyl substituent: one to the N-terminal amide carbonyl group, and the other to the primary amino group in the glucose moiety. 相似文献
3.
Ming-Daw Tsai Janet Weaver Heinz G. Floss Eric E. Conn Richard K. Creveling Mendel Mazelis 《Archives of biochemistry and biophysics》1978,190(2):553-559
The stereochemistry of the replacement of the SH-group of cysteine by CN catalyzed by β-cyanoalanine synthetase was studied using cysteine stereospecifically tritiated at C-3. Analysis of the resulting β-cyanoalanine by conversion into fumarate via aspartate and malate showed that the reaction had occurred with retention of configuration at C-3. Using cystine stereospecifically labeled at C-3 with tritium or with tritium and deuterium, it was found that the α,β-elimination reaction catalyzed by S-alkylcysteine lyase involves stereo-specific replacement of the β-substituent of the substrate by a hydrogen derived from the solvent, D2O or H2O, with retention of configuration to give pyruvate containing a chiral methyl group. The results are discussed, particularly in the light of mechanistic proposals by Braunstem and co-workers. 相似文献
4.
Yôsuke Mino 《Bioscience, biotechnology, and biochemistry》2013,77(1):211-212
The stereochemistry of some dihydrofurano-isoflavones previously isolated from white lupin roots, or obtained following fungal metabolism of prenylated isoflavones, was investigated using CD spectroscopy. The osmate ester/pyridine complex of dextrorotatory lupinisoflavone A (1) exhibited a positive CD Cotton effect at 480 nm, indicating a side-structure configuration (S at C- 2″), opposite to that of natural rotenone (9), which afforded a negative Cotton effect at 474 nm (R- configuration at C-2′ on the side structure [ring E]). The stereochemistry of the laevorotatory luteone metabolite BC-1 (2) and lupinisoflavone D (4) (both ^-configuration at C-2″) was similarly determined after converting to the corresponding dehydrate (10) or trimethyl-dehydrate (1b, 10a). 相似文献
5.
Besides the known eudesmanolides and oxepine derivatives we have isolated two new oxepine type sesquiterpene lactones from the roots of Smyrnium rotundifolium. The new compounds were smyrnicordi-8-enolide and isosmyrnicordiolide, its stereochemistry at C-8 and C-10 could not be established. 相似文献
6.
Ojima I Fumero-Oderda CL Kuduk SD Ma Z Kirikae F Kirikae T 《Bioorganic & medicinal chemistry》2003,11(13):2867-2888
A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions C-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN Mphi and the cytotoxicity against Mphi-like cells. 相似文献
7.
Else Lemmich 《Phytochemistry》1979,18(7):1195-1197
A new diterpenoid has been isolated from roots of Peucedanum oreoselinum. Mainly by spectroscopic methods, its structure is shown to be (+)-(E)-7-hydroxymethyl-2,6,10,14-tetramethyl-2,9,13-pentadecatrien-6-ol, yet without specification of stereochemistry at C-6 and C-7. Furthermore the roots afforded a high yield of falcarindiol, (+)-(Z)-heptadeca-1,9-dien-4,6-diyn-3,8-diol. 相似文献
8.
The side chain C-24 alkylation mechanism of phytosterols of Physarum polycephalum and Ochromonas danica, cultured in a nutrient medium containing methionine-CD3, has been studied. Depending on species, five or four deuterium atoms were incorporated respectively in C-24 ethyl phytosterols. No relation could be established between the stereochemistry of C-24 and the alkylation mechanism at this position. 相似文献
9.
Claus Schneider William E Boeglin Jeffery J Prusakiewicz Scott W Rowlinson Lawrence J Marnett Nigulas Samel Alan R Brash 《The Journal of biological chemistry》2002,277(1):478-485
Prostaglandin synthesis by cyclooxygenases-1 and -2 (COX-1 and COX-2) involves an initial oxygenation of arachidonic acid at C-11, followed by endoperoxide and cyclopentane ring formation, and then a second reaction with molecular oxygen in the S configuration at C-15. The resulting 15S-hydroxyl group of prostaglandins is crucial for their bioactivity. Using human COX-1 and human and murine COX-2, we have identified two amino acids located in the oxygenase active site that control the stereochemistry at C-15. The most crucial determinant is Ser-530, the residue that is acetylated by aspirin. In COX-2, site-directed mutagenesis of Ser-530 to methionine, threonine, or valine produced highly active enzymes that formed 82-95% 15R-configuration prostaglandins; these have the opposite stereochemistry at C-15 to the natural products. In COX-1, the corresponding Ser-530 mutations inactivated the enzyme. The second residue, Val-349, exerts a more subtle influence. When Val-349 was replaced by isoleucine, the mutant COX-1 and COX-2 enzymes formed 41 and 65% 15R-prostaglandins, respectively. This change was highly specific for isoleucine, as mutations of Val-349 to alanine, leucine, asparagine, or threonine did not alter or only slightly altered (< or =13%) the S-configuration at C-15. These results establish a previously unrecognized role for Ser-530 and Val-349 in maintaining the correct S stereochemistry of the carbon-15 hydroxyl group during prostaglandin synthesis. The findings may also explain the absolute conservation of Ser-530, the target of aspirin, throughout the families of cyclooxygenase enzymes. 相似文献
10.
Kim HS Khan SN Jadhav JR Jeong JW Jung K Kwak JH 《Bioorganic & medicinal chemistry letters》2011,21(13):3861-3865
A series of steroid-polyamine conjugates were synthesized and evaluated for their antimicrobial activity. This study was focused on the effect of stereochemistry at the C-3 and C-5 of steroids and types of polyamine at C-3 on activity against various human pathogens. All the conjugates exhibited strong antimicrobial activities against Gram-positive strains. Compound 18 was found to be the most potent in these series with a MIC value as low as 1 μg/mL against the bacterium Staphylococcus aureus ATCC6538P. 相似文献
11.
Letavic MA Bronk BS Bertsche CD Casavant JM Cheng H Daniel KL George DM Hayashi SF Kamicker BJ Kolosko NL Norcia LJ Oberton VD Rushing MA Santoro SL 《Bioorganic & medicinal chemistry letters》2002,12(19):2771-2774
The stereoselective synthesis of two novel series of tribasic macrocyclic antibiotics with potent in vitro activity against Pasteurella multocida and Escherichia coli strains of bacteria is described. The in vitro activity can be significantly influenced by the nature of the substituents on the C-4" aminoalcohol, with the stereochemistry of the C-4" alcohol playing a less critical role. The effect of substitution and stereochemistry on the in vivo activity in a murine model of respiratory infection is also described. 相似文献
12.
24-Methyl-5α-cholest-7-en-3β-ol (24-methyllathosterol) isolated from the seed oil of Helianthus annuus was shown to have 24α-configuration by 1H NMR spectroscopy. The stereochemistry at C-24 of some other 24-alkylsterols isolated from this plant material also was determined. 相似文献
13.
Polina I. Abronina 《Carbohydrate research》2009,344(2):240-244
A simple stereoselective synthesis of per-O-benzoyl-β-d-mannopyranosyl azide from per-O-benzoyl-α-d-mannopyranosyl bromide using phase transfer catalysis was developed. The stereochemistry at C-1 of the anomeric O-benzoylated α- and β-d-mannopyranosyl azides was unambiguously established using 2D NOESY NMR spectroscopy. Pure deprotected β-d-mannopyranosyl azide was prepared by debenzoylation with sodium methoxide in methanol. 相似文献
14.
Jie Liu Jun Shiono Kuniyoshi Shimizu Hongshan Yu Chunzhi Zhang Fengxie Jin Ryuichiro Kondo 《Bioorganic & medicinal chemistry letters》2009,19(12):3320-3323
Increased osteoclastic bone resorption plays a central role in the pathogenesis of many bone diseases, and osteoclast inhibitors are the most widely used treatments for these diseases. Ginsenosides, the main component of ginseng, have been known for their medicinal effects such as anti-inflammatory and anti-proliferative activities. In this study, we investigated the inhibitory effects of ginsenosides (ginsenoside 20(R)-Rh2 and ginsenoside 20(S)-Rh2) on osteoclastgenesis using RAW264 cells in vitro. Only ginsenoside 20(R)-Rh2 showed selective osteoclastgenesis inhibitory activity without any cytotoxicity up to 100 μM. These results implied that the stereochemistry of the hydroxyl group at C-20 may play an important role in selective osteoclastgenesis inhibitory activity. 相似文献
15.
A set of eight 1-hydroxyvitamin D3 compounds comprising the four possible (5Z)-1,3-diol stereoisomers and the corresponding (5E)-double bond isomers, has been prepared in order to assess the effect of 1,3-diol stereochemistry and 5,6-double bond geometry on binding affinity for the intestinal 1,25-(OH)2D3-receptor protein. The compounds were synthesized from either vitamin D3 or 3-epivitamin D3 via 3,5-cyclovitamin D intermediates. Competitive receptor binding assays establish that all changes from the natural ring A-configuration (1S, 3R, 5Z) lead to decreased binding affinity, and confirm the importance of the 1-hydroxy function since the conversion of stereochemistry at that center from 1α(S) to 1β(R) has the most pronounced effect on binding affinity (attenuation by more than three orders of magnitude). Other modifications (i.e., conversion at C-3, or cis to trans isomerization of the 5,6-double bond) decrease binding affinity by more moderate (ca. 10-fold) but cumulative factors. 相似文献
16.
Elise Champeil Manuel M. Paz Elaan Lukasiewicz Wan S. Kong Stephanie Watson Anne-Marie Sapse 《Bioorganic & medicinal chemistry letters》2012,22(23):7198-7200
We report here the synthesis of two amino precursors for the production of mitomycin C and 10-decarbamoylmitomycin C DNA adducts with opposite stereochemistry at C-1. The triamino mitosene precursors were synthesized in 5 steps from mitomycin C. In addition synthesis of the major mitomycin C-DNA adduct has been accomplished via coupling of a triaminomitosene with 2-fluoro-O6-(2-p-nitrophenylethyl)deoxyinosine followed by deprotection at the N2 and O6 positions. 相似文献
17.
Hartmut Kayser Philipp Eilinger Philippe Piechon Trixie Wagner 《Archives of biochemistry and biophysics》2011,(1):27
Hydroxylation of steroids at one of the side chain terminal methyl groups, commonly linked to C-26, represents an important regulatory step established in many phyla. Discrimination between the two sites, C-26 and C-27, requires knowing the stereochemistry of the products. 26-Hydroxylation of the insect steroid hormone 20-hydroxyecdysone by a microsomal cytochrome P450 was previously found to be responsible for hormonal resistance in a Chironomus cell line mainly producing the (25S)-epimer of 20,26-dihydroxyecdysone. Here, we studied the 25-desoxy analog of 20-hydroxyecdysone, ponasterone A, to elucidate the stereochemistry of the expected 26-hydroxy product, inokosterone, which occurs as C-25 epimers in nature. We identified the predominant metabolite as the C-25 R epimer of inokosterone on comparison by RP-HPLC with the (25R)- and (25S)-epimers the stereochemistry of which was confirmed by X-ray crystallography. (25R)-inokosterone was further oxidized to the 26-aldehyde identified by mass spectroscopy, borohydride reduction and metabolic transformation to 26-carboxylic acid. The (25S)-epimers of inokosterone and its aldehyde were minor products. With 20-hydroxyecdysone as substrate, we newly identified the (25R)-epimer of 20,26-dihydroxyecdysone as a minor product. In conclusion, the present stereochemical studies revealed high regioselectivity of the Chironomus enzyme to hydroxylate both steroids at the same methyl group, denoted C-27. 相似文献
18.
M Axelson 《Analytical biochemistry》1978,86(1):133-141
Simple and various O-substituted oxime derivatives of steroids may be interconverted by an acid-catalyzed reaction of the oxime with the appropriate substituted hydroxylamine hydrochloride in pyridine. For example, unsubstituted oximes of common hormonal steroids with keto groups in positions 3, 17, and 20 are converted into O-methyloximes by reaction of the oximes with 5 mg of methoxyamine hydrochloride in 50 μl of pyridine for 1 hr at 100°C. The reaction involves cleavage of the carbon-nitrogen bond and follows pseudo-first-order kinetics in the presence of excess reagent. The conversion of an oxime with a small O-substituent into one with a larger O-substituent was faster than the reverse reaction at the C-3 position. The rate of conversion depends on the position of the oxime function and decreases in the order: C-3 > C-20 > C-17 > C-11. The proximity and the configuration of other functional groups also influence the rates. Thus, determination of reaction rates with the aid of gas chromatography-mass spectrometry may be used to determine the positions of functional groups in steroids. The reactions are likely to be applieable to other groups of compounds possessing keto or aldehyde functions. 相似文献
19.
Ezio Bombardelli Attilio Bonati Bruno Gabetta Ernesto Martinelli Giuseppe Mustich Bruno Danieli 《Phytochemistry》1976,15(12):2021-2022
The structure of 17-O-acetyl-19,20-dihydrovoachalotine, a new alkaloid from the root bark of Voacanga chalotiana, has been determined by spectroscopic analysis. The stereochemistry at C-20 has been deduced on the basis of 13C-NMR and comparison with other compounds containing the voachalotine skeleton. 相似文献
20.
《Phytochemistry》1987,26(4):1065-1068
The structure and absolute stereochemistry of the new cytotoxic sesquiterpene lactones, tomenphantopin-A and -B, isolated from Elephantopus tomentosus, were determined from spectral data, chemical transformation and single-crystal X-ray analysis. Tomenphantopin-A and -B are two elephantopin-type germacranolides which possess an α-orientation of the oxygen substituent at C-2. 相似文献