- Design and synthesis of substrate-mimic inhibitors of mycothiol-S-conjugate amidase from Mycobacterium tuberculosis
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The Staudinger reaction between a polymer-supported triphenylphosphine reagent and pseudo-disaccharide azides is successfully applied to synthesize a variety of substrate-mimic mycothiol analogs. Screening of this new group of analogs against the mycobacterial detoxification enzyme mycothiol-S-conjugate amidase (MCA) yielded several modest inhibitors (IC50 values around 50 μM) and provided additional structure-activity relationships for future optimization of inhibitors of MCA and its homologs.
- Metaferia, Belhu B.,Ray, Satyajit,Smith, Jeremy A.,Bewley, Carole A.
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- Synthesis, photophysical properties, and photodynamic activity of positional isomers of TFPP-glucose conjugates
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The synthesis and characterization of a ‘complete set’ of positional isomers of tetrakis(perfluorophenyl)porphyrins (TFPP)-glucose conjugates (1OH, 2OH, 3OH, 4OH, and 6OH) are reported herein. The cellular uptake and photocytotoxicity of these conjugates were examined in order to investigate the influence of location of the TFPP moiety on the D-glucose molecule on the biological activity of the conjugates. An In vitro biological evaluation revealed that the certain of these isomers have a greater effect on cellular uptake and cytotoxicity than others. The TFPP-glucose conjugates 1OH, 3OH, and 4OH were found to exert exceptional photocytotoxicity in several types of cancer cells compared to 2OH and 6OH substituted isomers.
- Fadlan, Arif,Tanimoto, Hiroki,Ito, Tatsuya,Aritomi, Yusuke,Ueno, Maho,Tokuda, Masaya,Hirohara, Shiho,Obata, Makoto,Morimoto, Tsumoru,Kakiuchi, Kiyomi
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p. 1848 - 1858
(2018/03/06)
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- 3,4,6-Tri-O-acetyl-1,2-O-[1-(exo-ethoxy)ethyl-idene]-Β-d-manno- pyranose 0.11-hydrate
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The title compound, C16H24O10·0. 11H2O, is a key inter-mediate in the synthesis of 2-de-oxy-2-[ 18F]fluoro-d-glucose (18F-FDG), which is the most widely used mol-ecular-imaging probe for positron emission tomography (PET). The crystal structure has two independent mol-ecules (A and B) in the asymmetric unit, with closely comparable geometries. The pyran-ose ring adopts a 4 C 1 conformation [Cremer-Pople puckering parameters: Q = 0.553 (2) A?, = 16.2 (2)° and = 290.4 (8)° for mol-ecule A, and Q = 0.529 (2) A?, =15.3 (3)° and = 268.2 (9)° for mol-ecule B], and the dioxolane ring adopts an envelope conformation. The chiral centre in the dioxolane ring, introduced during the synthesis of the compound, has an R configuration, with the eth-oxy group exo to the manno-pyran-ose ring. The asymmetric unit also contains one water mol-ecule with a refined site-occupancy factor of 0.222 (8), which bridges between mol-ecules A and B via O - H?O hydrogen bonds.
- Liu, Ya-Ling,Zou, Pei,Wu, Hao,Xie, Min-Hao,Luo, Shi-Neng
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p. o338-o340
(2012/11/13)
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- A biosynthetic pathway for BE-7585A, a 2-thiosugar-containing angucycline-type natural product
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Sulfur is an essential element found ubiquitously in living systems. However, there exist only a few sulfur-containing sugars in nature and their biosyntheses have not been studied. BE-7585A produced by Amycolatopsis orientalis subsp. vinearia BA-07585 has a 2-thiosugar and is a member of the angucycline class of compounds. We report herein the results of our initial efforts to study the biosynthesis of BE-7585A. Spectroscopic analyses verified the structure of BE-7585A, which is closely related to rhodonocardin A. Feeding experiments using 13C-labeled acetate were carried out to confirm that the angucycline core is indeed polyketide-derived. The results indicated an unusual manner of angular tetracyclic ring construction, perhaps via a Baeyer-Villiger type rearrangement. Subsequent cloning and sequencing led to the identification of the bex gene cluster spanning ～30 kbp. A total of 28 open reading frames, which are likely involved in BE-7585A formation, were identified in the cluster. In view of the presence of a homologue of a thiazole synthase gene (thiG), bexX, in the bex cluster, the mechanism of sulfur incorporation into the 2-thiosugar moiety could resemble that found in thiamin biosynthesis. A glycosyltransferase homologue, BexG2, was heterologously expressed in Escherichia coli. The purified enzyme successfully catalyzed the coupling of 2-thioglucose 6-phoshate and UDP-glucose to produce 2-thiotrehalose 6-phosphate, which is the precursor of the disaccharide unit in BE-7585A. On the basis of these genetic and biochemical experiments, a biosynthetic pathway for BE-7585A can now be proposed. The combined results set the stage for future biochemical studies of 2-thiosugar biosynthesis and BE-7585A assembly.
- Sasaki, Eita,Ogasawara, Yasushi,Liu, Hung-Wen
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experimental part
p. 7405 - 7417
(2010/08/05)
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- Synthesis of the positron-emitting radiotracer [18F]-2-fluoro-2- deoxy-d-glucose from resin-bound perfluoroalkylsulfonates
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A new approach to the synthesis of 2-fluoro-2-deoxy-d-glucose (FDG, [ 19/18F]-3) is described, which employs supported perfluoroalkylsulfonate precursors 33-36, where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [ 19F]fluoride ion afforded protected FDG [19F]-18 as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [19F]-18 was shown to produce [19F]FDG. The method has been applied to the efficient radiosynthesis of the imaging agent [18F]FDG, and was shown to produce the radiochemical tracer in good radiochemical yield (average 73%, decay corrected). The Royal Society of Chemistry 2009.
- Brown, Lynda J.,Ma, Nianchun,Bouvet, Denis R.,Champion, Sue,Gibson, Alex M.,Hu, Yulai,Jackson, Alex,Khan, Imtiaz,Millot, Nicolas,Topley, Amy C.,Wadsworth, Harry,Wynn, Duncan,Brown, Richard C. D.
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scheme or table
p. 564 - 575
(2009/07/18)
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- From glycoside hydrolases to thioglycoligases: The synthesis of thioglycosides
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The treatment of various glycosyl acceptors, each containing a reactive thiol group, with the appropriate glycosyl donor and a glycoside hydrolase or glycosynthase, failed to yield any thioglycosides - only the products of O-glycosylation were formed. However, thioglycosides were formed when a thioglycoligase was used to mediate the reaction between acceptor and donor. In fact, pyranose acceptors possessing a thiol group at C3, C4 or C6 (but not C2) were all capable of conversion into thioglycosides. Some comment is given regarding the mechanism of the various processes.
- Stick, Robert V.,Stubbs, Keith A.
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p. 321 - 335
(2007/10/03)
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- Sulfinyl hexose derivatives useful for glycosylation
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Hexose derivatives are described which facilitate control over the stereochemistry of the glycosyl bond formed in the course of a solid phase glycosylation reaction. Methods for their use are also described.
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- Di- and tri-saccharide glycosyl donors for the synthesis of fragments of the O-specific antigen of Shigella dysenteriae type 1
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Methyl O-(2,4-di-O-benzoyl-3-O-bromoacetyl-α-L-rhamnopyranosyl)-(1->3)-2,4-di-O-benzoyl-α-L-rhamnopyranoside was treated with dichloromethyl methyl ether and ZnCl2 to give O-(2,4-di-O-benzoyl-3-O-bromoacetyl-α-L-rhamnopyranosyl)-(1->3)-2,4-di-O-benzoyl-α-L-rhamnopyranosyl chloride.Similar treatment of methyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1->3)-2,4-di-O-benzoyl-α-L-rhamnopyranoside (13) gave crystalline O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1->3)-2,4-di-O-benzoyl-α-L-rhamnosyl chloride (14), which was also obtained by treatment of methyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1->3)-2,4-di-O-benzoyl-1-thio-α-L-rhamnopyranoside (12) with chlorine.In contrast to the conversion 12 -> 14, which was stereospecific, the reaction of methyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1->3)-(O-2,4-di-O-benzoyl-α-L-rhamnopyranosyl)-(1->3)-2,4-di-O-benzoyl-1-thio-α-L-rhamnopyranoside with chlorine gave a mixture of the corresponding α- (16) and (β)- 17 glycosyl chlorides.Condensation of the mixed chlorides 16 and 17 with 1,3,4,6-tetra-O-acetyl-α-D-galactopyranose, followed by reduction-acetylation of the product, gave a fully protected derivative of the tetrasaccharide of α-D-GlcpNAc-(1->3)-α-L-Rhap-(1->3)-α-L-Rhap-(1->2)-α-D-Galp.
- Kovac, Pavol
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p. 219 - 231
(2007/10/02)
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- Synthesis of tetrasaccharide building block of the O-specific polysaccharide of Shigella dysenteriae type 1
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A glycosyl trichloroacetimidate derivative (1) of the tetrasaccharide α-D-Galp-(1→3)-α-D-GlcpNAc-(1→3)-α-L-Rhap-(1→3)-α-L-Rhap was synthesized in a highly stereoselective, stepwise manner, using methyl 1-thioglycosides of L-rhamnose, 2-azido-2-deoxy-D-glucose and D-galactose, as major intermediates. The protecting group scenario in compound 1 permits regioselective deblocking at its 'non-reducing end' unit. Therefore 1 is a suitable intermediate for the preparation of extended fragments of the title polysaccharide.
- Pozsgay,Glaudemans,Robbins,Schneerson
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p. 10249 - 10264
(2007/10/02)
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- PHASE-TRANSFER CATALYSED SYNTHESIS OF 4-S-β-D-GLUCOPYRANOSYL-4-THIO-D-GLUCOPYRANOSE (THIOCELLOBIOSE) AND 2-S-β-D-GLUCOPYRANOSYL-2-THIO-D-GLUCOPYRANOSE (THIOSOPHOROSE)
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Syntheses of the potential enzyme-inducers thiocellobiose (7) and thiosophorose (11) ara described.The intermediates methyl 2,3,6-tri-O-benzoyl-4-O-trifluoromethylsulfonyl-α-D-galactopyranoside and 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethylsulfonyl-β-D-mannopyranose were obtained in good yield from methyl α-D-galactopyranoside or 1,3,4,6-tetra-O-acetyl-β-D-mannopyranose.The stereoselective reaction of triflates with the sodium salt of 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose was performed under phase-transfer conditions.Transesterification of methyl 2,3,6-tri-O-benzoyl-4-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-thio-β-D-glucopyranoside (after selective acetolysis) and 1,3,4,6-tetra-O-acetyl-2-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-thio-β-D-glucopyranose afforded 7 and 11.
- Hamacher, Kurt
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p. 291 - 296
(2007/10/02)
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