| 1. |
- Ruda, K., et al.
(författare)
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Synthesis of the Leishmania LPG core heptasaccharyl myo-inositol
- 2000
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 122:45, s. 11067-11072
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Tidskriftsartikel (refereegranskat)abstract
- Total synthesis of the core heptasaccharyl myo-inositol, Galp(a1-6)Galp(a1-3)Galf(ß1-3)[Glcp(a1-PO4-6)Manp](a1-3)Manp(a1-4)GlcN p(a1-6)Ins-1-PO4, and the corresponding hexasaccharyl myo-inositol, Galp(a1-6)Galp(a1-3)Galf(ß1-3)Manp(a1-3)Manp(a1-4)GlcNp(a1-6)Ins-1-PO4 , found in the lipophosphoglycans of Leishmania parasites are described. The target molecules contain synthetic challenges such as an unusual internal galactofuranosyl residue and an anomeric phosphodiester. The synthesis was accomplished using a convergent block synthetic strategy. Four building blocks, a trigalactoside, a dimannoside, a glucosyl inositolphosphate, and a glucosyl-a-1-H-phosphonate, all appropriately protected, were used. The trigalactoside was linked to the dimannoside followed by glycosylation with the glucosyl inositolphosphate to produce the fully protected hexasaccharyl myo-inositol. Subsequent oxidative coupling of the glucosyl-H-phosphonate formed the anomeric phosphodiester linkage to produce the protected heptasaccharyl myo-inositol. Both the assembly order of the subunits and sequence of deprotection were essential for the successful synthesis of these complex molecules. The deprotection was accomplished by deacetylation and clevage of benzyl ethers with sodium in liquid ammonia, followed by acidic deacetalization/desilylation to produce the target molecules.
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| 2. |
- Garegg, P.J., et al.
(författare)
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Transglucosidation of methyl and ethyl D-glucopyranosides by alcoholysis
- 2002
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Ingår i: Carbohydrate Research. - 0008-6215 .- 1873-426X. ; 337:6, s. 517-521
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Tidskriftsartikel (refereegranskat)abstract
- The transglucosidations of methyl 4-O-methyl-a- and -ß-D-glucopyranoside in ethanolic camphor-10-sulfonic acid, and of ethyl 4-O-methyl-a- and -ß-D-glucopyranoside in methanolic camphor-10-sulfonic acid, have been studied. Samples were removed at intervals and the proportions of the glucosides determined by GC of their acetates. The results show that the anomer with the inverted configuration predominates in the initially formed product (˜59-70%). This indicates that all the studied reactions proceed via the same mechanism, involving exocyclic C-O cleavage and formation of a glucopyranosylium ion, but that the eliminated alcohol exerts some steric hindrance, which favors the approach of the other alcohol from the opposite side. © 2002 Published by Elsevier Science Ltd.
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| 3. |
- Lindberg, Jan, et al.
(författare)
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Efficient routes to glucosamine-myo-inositol derivatives, key building blocks in the synthesis of glycosylphosphatidylinositol anchor substances
- 2002
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Ingår i: Tetrahedron. - 0040-4020 .- 1464-5416. ; 58:7, s. 1387-1398
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Tidskriftsartikel (refereegranskat)abstract
- Short synthetic routes to protected derivatives of 2-amino-2-deoxy-a-D-glucopyranosyl-(1?6)-D-myo-inositol are described. Various 2-azido-2-deoxy-glucosyl donors were synthesized, starting from D-glucal or glucosamine hydrochloride. Derivatives of 1,2- and 2,3- D-myo-inositol-camphanylidene acetals were prepared to function as glycosyl acceptors. The subsequent glycosylations produced useful building blocks for the synthesis of GPI-anchor substances. © 2002 Elsevier Science Ltd. All rights reserved.
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| 4. |
- Lindberg, Jan, et al.
(författare)
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Synthesis of galactoglycerolipids found in the HT29 human colon carcinoma cell line
- 2002
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Ingår i: Tetrahedron. - 0040-4020 .- 1464-5416. ; 58:25, s. 5109-5117
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis of three galactoglycerolipids (3-O-(ß-D-galactopyranosyl)-1-O-hexadecyl-2-O-palmitoyl-sn-glycerol, 3-O-(a-D-galactopyranosyl-(1?4)-ß-D-galactopyranosyl)-1-O- hexadecyl-2-O-palmitoyl-sn-glycerol, 3-O-(a-D-galactopyranosyl-(1?4)-ß-D-galactopyranosyl)-1-O- hexadecyl-sn-glycerol), and the corresponding glycerolipid (1-O-hexadecyl-2-O-palmitoyl-sn-glycerol) is described. The first two compounds were recently identified in the human colon carcinoma cell line HT29. The three-carbon synthon (S)-glycidol was used for construction of the glycerol moiety. Glycosylation of (S)-glycidol with protected galactosyl and digalactosyl donors produced galactosyl and digalactosyl glycidols. Lewis acid catalyzed opening of the epoxide produced protected galactosyl and digalactosyl glycerolipids. Deprotection, or palmitoylation followed by deprotection, yielded the target compounds. The corresponding glycerolipid was synthesized analogously and an oxidation-reduction procedure for tritiation was developed. The synthesized compounds will be used in studies of the role of galactosyl glycerolipids in differentiation and colon cancer development. © 2002 Elsevier Science Ltd. All rights reserved.
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| 5. |
- Nilsson, Ulrika K., et al.
(författare)
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Lack of stereospecificity in lysophosphatidic acid enantiomerinduced calcium mobilization in human erythroleukemia cells
- 2003
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Ingår i: Lipids. - 0024-4201. ; 38:10, s. 1057-1064
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Tidskriftsartikel (refereegranskat)abstract
- Lysophosphatidic acid (LPA) is a lipid mediator that, among several other cellular responses, can stimulate cells to mobilize calcium (Ca2+). LPA is known to activate at least three different subtypes of G protein-coupled receptors. These receptors can then stimulate different kinds of G proteins. In the present study, LPA and LPA analogs were synthesized from (R)- and (S)-glycidol and used to characterize the ability to stimulate Ca2+ mobilization. The cytosolic Ca2+ concentration ([Ca2+]i) was measured in fura-2-acetoxymethylester-loaded human erythroleukemia (HEL) cells. Furthermore, a reverse transcriptase polymerase chain reaction was used to characterize LPA receptor subtypes expressed in HEL cells. The results show that HEL cells mainly express LPA1 and LPA2, although LPA3 might possibly be expressed as well. Moreover, LPA and its analogs concentration-dependently increased [Ca2+]i in HEL cells. The response involved both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores. This is the first time the unnatural (S)-enantiomer of LPA, (S)-3-O-oleoyl-1-O-phosphoryl-glycerol, has been synthesized and studied according to its ability to activate cells. The results indicate that this group of receptors does not discriminate between (R)- and (S)-enantiomers of LPA and its analogs. When comparing ether analogs having different hydrocarbon chain lengths, the tetradecyl analog (14 carbons) was found to be the most effective in increasing [Ca2+]i. Pertussis toxin treatment of the HEL cells resulted in an even more efficient Ca2+ mobilization stimulated by LPA and its analogs. Furthermore, at repeated incubation with the same ligand no further increase in [Ca2+]i was obtained. When combining LPA with the ether analogs no suppression of the new Ca2+ signal occurred. All these findings may be of significance in the process of searching for specific agonists and antagonists of the LPA receptor subtypes.
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| 6. |
- Ruda, K., et al.
(författare)
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Synthesis of an inositol phosphoglycan fragment found in Leishmania parasites
- 2000
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Ingår i: Tetrahedron. - 0040-4020 .- 1464-5416. ; 56:24, s. 3969-3975
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis of 1 and 2a is described using a block synthetic strategy. Compound 4 was used as precursor for the two mannose derivatives which, coupled together, forms the dimannoside building block. Thioglycoside 7 was coupled to 8 yielding inositol phosphoglycan 9a, which was selectively deprotected and reacted with 2,3,4,6-tetra-O-benzyl-a-D-glucopyranos-1-yl H- phosphonate to form the protected target molecule 12. Deprotection of 12 by acidic deacetalisation/desilylation and subsequent catalytic hydrogenolysis resulted in cleavage of the anomeric phosphodiester to produce 1. Debenzylation with sodium in liquid ammonia followed by acidic deacetalisation/desilylation gave the target compound 2a. (C) 2000 Published by Elsevier Science Ltd.
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