The Experts below are selected from a list of 684 Experts worldwide ranked by ideXlab platform
Stefan Oscarson - One of the best experts on this subject based on the ideXlab platform.
-
variant synthetic pathway to glucuronic acid containing di and trisaccharide Thioglycoside building blocks for continued synthesis of cryptococcus neoformans capsular polysaccharide structures
Carbohydrate Research, 2008Co-Authors: Jan Vesely, Lina Rydner, Stefan OscarsonAbstract:Abstract An alternative pathway to glucuronic acid-containing di- and trisaccharide Thioglycoside building blocks, suitable for the synthesis of Cryptococcus neoformans capsular polysaccharide structures, has been developed. As opposed to our earlier synthesis, this approach features the introduction of the glucuronic acid motif at the di- and trisaccharide level through oxidation of a glucose residue. This approach circumvents problems encountered in glycosylations with glucuronic acid donors and benzylation of glucuronic acid-containing derivatives. Selective protection of primary alcohols was obtained at the di- and trisaccharide stage using TBDMS or trityl protecting groups, respectively. After benzylation of the secondary hydroxyl groups and subsequent removal of the TBDMS or trityl group, oxidation of the free primary alcohols to carboxylic acids was performed in high yield using the TEMPO–BAIB reagent mixture, which does not tend to oxidize Thioglycosides. The new approach requires a number of extra steps, but has proven to be more reliable and easily reproducible.
-
synthesis of fused bicyclic Thioglycosides of n acylated glucosamine as analogues of mycothiol
Carbohydrate Research, 2007Co-Authors: Rikard Slattegard, David W Gammon, Stefan OscarsonAbstract:The synthesis of a fused bicyclic Thioglycoside analogue of mycothiol, (3R)-3-acetylamino-4-one-6,7-dihydro-(1',2'-dideoxy-beta-D-glucopyranoso)[2',1'-f]-1,5-thiazepane (5), is reported. Treatment of phthalimido-protected peracetylated glucosamine with N-acetyl-cysteine and boron trifluoride-etherate gave the beta-linked Thioglycoside, which was deprotected and cyclized, using HOBt and EDCl to form the lactam and giving the target structure. This mycothiol mimic and its tri-O-acetate will be investigated as potential inhibitors of enzymes involved in the biosynthesis of mycothiol. The protected derivative also has the potential to be an alpha-selective N-cysteinyl glucosamine donor; however, initial glycosylation attempts failed due to the apparent stability of the fused bicyclic system.
-
synthesis of cryptococcus neoformans capsular polysaccharide structures iv construction of Thioglycoside donor blocks and their subsequent assembly
Journal of Carbohydrate Chemistry, 2003Co-Authors: Mia Alpe, Stefan Oscarson, Par SvahnbergAbstract:Di‐ and trisaccharide Thioglycoside building blocks, ethyl (2,3,4‐tri‐O‐benzyl‐β‐d‐xylopyranosyl)‐(1→2)‐3‐O‐allyl‐4,6‐di‐O‐benzyl‐1‐thio‐α‐d‐mannopyranoside, ethyl (2,3,4‐tri‐O‐benzyl‐β‐d‐xylopyranosyl)‐(1→2)‐6‐O‐acetyl‐3‐O‐allyl‐4‐O‐benzyl‐1‐thio‐α‐d‐mannopyranoside and ethyl (2,3,4‐tri‐O‐benzyl‐β‐d‐xylopyranosyl)‐(1→4)‐[(2,3,4‐tri‐O‐benzyl‐β‐d‐xylopyranosyl)‐(1→2)]‐3‐O‐allyl‐6‐O‐benzyl‐1‐thio‐α‐d‐mannopyranoside, corresponding to repetitive structures in the capsular polysaccharide (CPS) of Cryptococcus neoformans have been synthesised using silver triflate‐promoted couplings between benzobromoxylose and properly protected mannose ethyl Thioglycosides. The blocks contain an orthogonal allyl group in the 3‐position of the mannose residue to allow continued formation of the (1→3)‐linked mannan backbone of the CPS. They have benzyl ethers as persistent protecting groups to facilitate access to the acetylated target structures. Assembly of the blocks employing DMTST as promoter in diethyl ether afforded in ...
-
synthesis of uronic acid containing xylans found in wood and pulp
Journal of The Chemical Society-perkin Transactions 1, 2001Co-Authors: Stefan Oscarson, Par SvahnbergAbstract:Two uronic acid-containing trisaccharides, (4-deoxy-β-L-threo-hex-4-enopyranosyluronic acid)- and (4-O-methyl-α-D-gluropyranosyluronic acid)-(1→2)-β-D-xylopyranosyl-(1→4)-D-xylopyranose, found in enzyme hydrolysates from pulp are synthesised. A common dixyloside 2′-OH acceptor, p-methoxyphenyl [3,4-O-(2′,3′-dimethoxybutane-2′,3′-diyl)-β-D-xylopyranosyl]-(1→4)-2,3-di-O-benzoyl-β-D-xylopyranoside, is constructed and coupled with two glucuronate Thioglycoside donors differently substituted in the 4-position, O-methyl and O-mesyl, respectively, to give trisaccharides. DMTST as promoter in diethyl ether gives exclusively the α-linked products in high yield. Treatment of the 4″-O-mesyl trisaccharide with DBU then gives the α,β-unsaturated uronic acid derivative. The protection pattern introduced in the acceptor allows continued synthesis of larger oligosaccharides. Removal of the butanedione acetal produces 3′,4′-acceptors, and the p-methoxyphenyl glycoside can be transformed into various glycosyl donors, e.g. Thioglycosides and sugar halides. Complete deprotection gives the two target reducing trisaccharides.
-
Synthesis of a d,d- and l,d-heptose-containing hexasaccharide corresponding to a structure from Haemophilus ducreyi lipopolysaccharides
Tetrahedron: Asymmetry, 2000Co-Authors: Christian Bernlind, Simon Bennett, Stefan OscarsonAbstract:Abstract The synthesis of a linear hexasaccharide, 2-(4-trifluoroacetamidophenyl)ethyl (β- d -galactopyranosyl)-(1→4)-(2-acetamido-2-deoxy-β- d -glucopyranosyl)-(1→3)-(β- d -galactopyranosyl)-(1→4)-( d - glycero -α- d - manno -heptopyranosyl)-(1→6)-(β- d -glucopyranosyl)-(1→4)- l - glycero -α- d - manno -heptopyranoside, corresponding to a structure found in Haemophilus ducreyi LPS, is described. A Barbier reaction between benzyloxymethyl chloride and a properly protected 6-aldo-1-thio-mannopyranoside yielded both the d , d - and the l , d -heptopyranoside ( 2 and 3 , ratio 2:3), which were separated and both used in the synthesis. p -Methoxybenzyl and chloroacetyl groups were employed as temporary protecting groups, selectively removed in the presence of the persistent benzyl, acetyl, benzoyl and isopropylidene groups by treatment with DDQ/H 2 O and hydrazine dithiocarbonate, respectively. Thioglycosides were utilised as donors throughout using either NIS/TfOH or DMTST as promoters. The introduction of the spacer into Thioglycoside 5 was high-yielding (95%) but with low stereoselectivity (α:β 5:3). All other glycosylations are completely stereoselective. The target hexasaccharide is obtained via a 3+3 block approach with the yield in the final NIS/TfOH-promoted coupling between an N , N -diacetyl-trisaccharide thioglycosyl donor 20 and a 4′′-OH trisaccharide acceptor 13 being 75%.
John M Gardiner - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of l iduronic acid derivatives via 3 2 1 and 2 2 2 l iduronic lactones from bulk glucose derived cyanohydrin hydrolysis a reversible conformationally switched superdisarmed rearmed lactone route to heparin disaccharides
Journal of Organic Chemistry, 2015Co-Authors: Steen U Hansen, Charlotte E Dalton, Marek Barath, Glenn Kwan, James Raftery, Gordon C Jayson, Gavin J Miller, John M GardinerAbstract:l-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of l-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] l-iduronate lactones. The former is obtained via a 100 g scale synthesis of 3-OBn l-IdoA. A two-step conversion of this mixture provides either pure anomer of the novel [2.2.2] l-iduronate Thioglycoside lactones. Both [3.2.1] and [2.2.2] lactones are converted into GlcN-IdoA heparin precursor disaccharides. The [2.2.2] lactone enables a scalable 3-step route from 1 to a new type of highly disarmed O-4 iduronate Thioglycoside, which is an effective acceptor with glucoazide Thioglycoside donors. The resulting new iduronic [2.2.2] lactone disaccharides are readily rearmed by mild methanolysis to provide GlcN-IdoA thiophenyl disaccharide donors, intercepting their established utility for the assembly of both heparin- and heparan sulfate-like oligosaccharides. The [2.2.2] lactonization acts as a conformational switch to superdisarm iduronate components, reversible by lactone ring opening. In addition, the separated 2,4-diacetates also provide short access to all four anomeric and ring size isomers of l-iduronic acid methyl glycosides, including the first syntheses of the parent idofuranosides. X-ray structures are reported for a [2.2.2] iduronate lactone and examples of both methyl l-idopyranoside and novel methyl-l-idofuranoside systems.
-
Synthesis of l‑Iduronic Acid Derivatives via [3.2.1] and [2.2.2] l‑Iduronic Lactones from Bulk Glucose-Derived Cyanohydrin Hydrolysis: A Reversible Conformationally Switched Superdisarmed/Rearmed Lactone Route to Heparin Disaccharides
2015Co-Authors: Steen U. Hansen, Charlotte E Dalton, Glenn Kwan, James Raftery, Gavin J Miller, Marek Baráth, Gordon C. Jayson, John M GardinerAbstract:l-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of l-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] l-iduronate lactones. The former is obtained via a 100 g scale synthesis of 3-OBn l-IdoA. A two-step conversion of this mixture provides either pure anomer of the novel [2.2.2] l-iduronate Thioglycoside lactones. Both [3.2.1] and [2.2.2] lactones are converted into GlcN-IdoA heparin precursor disaccharides. The [2.2.2] lactone enables a scalable 3-step route from 1 to a new type of highly disarmed O-4 iduronate Thioglycoside, which is an effective acceptor with glucoazide Thioglycoside donors. The resulting new iduronic [2.2.2] lactone disaccharides are readily rearmed by mild methanolysis to provide GlcN-IdoA thiophenyl disaccharide donors, intercepting their established utility for the assembly of both heparin- and heparan sulfate-like oligosaccharides. The [2.2.2] lactonization acts as a conformational switch to superdisarm iduronate components, reversible by lactone ring opening. In addition, the separated 2,4-diacetates also provide short access to all four anomeric and ring size isomers of l-iduronic acid methyl glycosides, including the first syntheses of the parent idofuranosides. X-ray structures are reported for a [2.2.2] iduronate lactone and examples of both methyl l-idopyranoside and novel methyl-l-idofuranoside systems
-
synthesis and scalable conversion of l iduronamides to heparin related di and tetrasaccharides
Journal of Organic Chemistry, 2012Co-Authors: Steen U Hansen, Marek Barath, James Raftery, Gordon C Jayson, Gavin J Miller, Karl R Broberg, Egle Avizienyte, Madeleine Helliwell, John M GardinerAbstract:A diastereomerically pure cyanohydrin, preparable on kilogram scale, is efficiently converted in one step into a novel l-iduronamide. A new regioselective acylation of this iduronamide and a new mild amide hydrolysis method mediated by amyl nitrite enables short, scalable syntheses of an l-iduronate diacetate C-4 acceptor, and also l-iduronate C-4 acceptor Thioglycosides. Efficient conversions of these to a range of heparin-related gluco-ido disaccharide building blocks (various C-4 protection options) including efficient multigram access to key heparin-building block ido-Thioglycoside donors are described. A 1-OAc disaccharide is converted into a heparin-related tetrasaccharide, via divergence to both acceptor and donor disaccharides. X-ray and NMR data of the 1,2-diacetyl iduronate methyl ester and the analogous iduronamide show that while both adopt 1C4 conformations in solution, the iduronate ester adopts the 4C1 conformation in solid state. An X-ray structure is also reported for the novel, 4C1-confo...
-
Synthesis and Scalable Conversion of l‑Iduronamides to Heparin-Related Di- and Tetrasaccharides
2012Co-Authors: Steen U. Hansen, James Raftery, Gordon C Jayson, Gavin J Miller, Karl R Broberg, Egle Avizienyte, Madeleine Helliwell, Marek Baráth, John M GardinerAbstract:A diastereomerically pure cyanohydrin, preparable on kilogram scale, is efficiently converted in one step into a novel l-iduronamide. A new regioselective acylation of this iduronamide and a new mild amide hydrolysis method mediated by amyl nitrite enables short, scalable syntheses of an l-iduronate diacetate C-4 acceptor, and also l-iduronate C-4 acceptor Thioglycosides. Efficient conversions of these to a range of heparin-related gluco-ido disaccharide building blocks (various C-4 protection options) including efficient multigram access to key heparin-building block ido-Thioglycoside donors are described. A 1-OAc disaccharide is converted into a heparin-related tetrasaccharide, via divergence to both acceptor and donor disaccharides. X-ray and NMR data of the 1,2-diacetyl iduronate methyl ester and the analogous iduronamide show that while both adopt 1C4 conformations in solution, the iduronate ester adopts the 4C1 conformation in solid state. An X-ray structure is also reported for the novel, 4C1-conformationally locked bicyclic 1,6-anhydro iduronate lactone along with an X-ray structures of a novel distorted 4C1 iduronate 4,6-lactone. Deuterium labeling also provides mechanistic insight into the formation of lactone products during the novel amyl nitrite-mediated hydrolysis of iduronamide into the parent iduronic acid functionality
Martin A. Fascione - One of the best experts on this subject based on the ideXlab platform.
-
mechanistic studies on a sulfoxide transfer reaction mediated by diphenyl sulfoxide triflic anhydride
Chemistry: A European Journal, 2012Co-Authors: Martin A. Fascione, Sophie J. Adshead, Pintu K. Mandal, Colin A. Kilner, Andrew G. Leach, Bruce W TurnbullAbstract:Sulfoxides are frequently used in organic synthesis as chiral auxiliaries and reagents to mediate a wide variety of chemical transformations. For example, diphenyl sulfoxide and triflic anhydride can be used to activate a wide range of glycosyl donors including hemiacetals, glycals and Thioglycosides. In this way, an alcohol, enol or sulfide is converted into a good leaving group for subsequent reaction with an acceptor alcohol. However, reaction of diphenyl sulfoxide and triflic anhydride with oxathiane-based Thioglycosides, and other oxathianes, leads to a different process in which the Thioglycoside is oxidised to a sulfoxide. This unexpected oxidation reaction is very stereoselective and proceeds under anhydrous conditions in which the diphenyl sulfoxide acts both as oxidant and as the source of the oxygen atom. Isotopic labelling experiments support a reaction mechanism that involves the formation of oxodisulfonium (S-O-S) dication intermediates. These intermediates undergo oxygen-exchange reactions with other sulfoxides and also allow interconversion of axial and equatorial sulfoxides in oxathiane rings. The reversibility of the oxygen-exchange reaction suggests that the stereochemical outcome of the oxidation reaction may be under thermodynamic control, which potentially presents a novel strategy for the stereoselective synthesis of sulfoxides.
-
Mechanistic Studies on a Sulfoxide Transfer Reaction Mediated by Diphenyl Sulfoxide/Triflic Anhydride
Chemistry - A European Journal, 2012Co-Authors: Martin A. Fascione, Sophie J. Adshead, Pintu K. Mandal, Colin A. Kilner, Andrew G. Leach, W. Bruce TurnbullAbstract:Sulfoxides are frequently used in organic synthesis as chiral auxiliaries and reagents to mediate a wide variety of chemical transformations. For example, diphenyl sulfoxide and triflic anhydride can be used to activate a wide range of glycosyl donors including hemiacetals, glycals and Thioglycosides. In this way, an alcohol, enol or sulfide is converted into a good leaving group for subsequent reaction with an acceptor alcohol. However, reaction of diphenyl sulfoxide and triflic anhydride with oxathiane-based Thioglycosides, and other oxathianes, leads to a different process in which the Thioglycoside is oxidised to a sulfoxide. This unexpected oxidation reaction is very stereoselective and proceeds under anhydrous conditions in which the diphenyl sulfoxide acts both as oxidant and as the source of the oxygen atom. Isotopic labelling experiments support a reaction mechanism that involves the formation of oxodisulfonium (S-O-S) dication intermediates. These intermediates undergo oxygen-exchange reactions with other sulfoxides and also allow interconversion of axial and equatorial sulfoxides in oxathiane rings. The reversibility of the oxygen-exchange reaction suggests that the stereochemical outcome of the oxidation reaction may be under thermodynamic control, which potentially presents a novel strategy for the stereoselective synthesis of sulfoxides.
Jinsong Yang - One of the best experts on this subject based on the ideXlab platform.
-
stereodirecting effect of c5 carboxylate substituents on the glycosylation stereochemistry of 3 deoxy d manno oct 2 ulosonic acid kdo Thioglycoside donors stereoselective synthesis of α and β kdo glycosides
Journal of the American Chemical Society, 2018Co-Authors: Wei Huang, Yingyu Zhou, Xingling Pan, Xianyang Zhou, Jincai Lei, Dongmei Liu, Yue Chu, Jinsong YangAbstract:The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) ethyl Thioglycoside donors is presented. The coupling of 5-O-arylcarbonyl or acetyl protected Kdo Thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5-O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo Thioglycoside donors is switchable: (1) The glycosylation of the 5-O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete β-stereoselectivity, furnishing the corresponding β-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate ...
-
Stereodirecting Effect of C5-Carboxylate Substituents on the Glycosylation Stereochemistry of 3‑Deoxy‑d-manno-oct-2-ulosonic Acid (Kdo) Thioglycoside Donors: Stereoselective Synthesis of α- and β‑Kdo Glycosides
2018Co-Authors: Wei Huang, Yingyu Zhou, Xingling Pan, Xianyang Zhou, Jincai Lei, Dongmei Liu, Yue Chu, Jinsong YangAbstract:The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) ethyl Thioglycoside donors is presented. The coupling of 5-O-arylcarbonyl or acetyl protected Kdo Thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5-O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo Thioglycoside donors is switchable: (1) The glycosylation of the 5-O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete β-stereoselectivity, furnishing the corresponding β-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate acceptors, while the selectivity may switch to predominant β in the glycosylation of the 5-O-4-nitropicoloyl carrying donor with more reactive secondary alcohols. The synthetic use of the newly developed Kdo donors 1c and 7b has been demonstrated by facile preparation of a structurally unique trisaccharide motif 19 which possesses both α- and β-Kdo glycosidic bonds
Steen U Hansen - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of l iduronic acid derivatives via 3 2 1 and 2 2 2 l iduronic lactones from bulk glucose derived cyanohydrin hydrolysis a reversible conformationally switched superdisarmed rearmed lactone route to heparin disaccharides
Journal of Organic Chemistry, 2015Co-Authors: Steen U Hansen, Charlotte E Dalton, Marek Barath, Glenn Kwan, James Raftery, Gordon C Jayson, Gavin J Miller, John M GardinerAbstract:l-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of l-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] l-iduronate lactones. The former is obtained via a 100 g scale synthesis of 3-OBn l-IdoA. A two-step conversion of this mixture provides either pure anomer of the novel [2.2.2] l-iduronate Thioglycoside lactones. Both [3.2.1] and [2.2.2] lactones are converted into GlcN-IdoA heparin precursor disaccharides. The [2.2.2] lactone enables a scalable 3-step route from 1 to a new type of highly disarmed O-4 iduronate Thioglycoside, which is an effective acceptor with glucoazide Thioglycoside donors. The resulting new iduronic [2.2.2] lactone disaccharides are readily rearmed by mild methanolysis to provide GlcN-IdoA thiophenyl disaccharide donors, intercepting their established utility for the assembly of both heparin- and heparan sulfate-like oligosaccharides. The [2.2.2] lactonization acts as a conformational switch to superdisarm iduronate components, reversible by lactone ring opening. In addition, the separated 2,4-diacetates also provide short access to all four anomeric and ring size isomers of l-iduronic acid methyl glycosides, including the first syntheses of the parent idofuranosides. X-ray structures are reported for a [2.2.2] iduronate lactone and examples of both methyl l-idopyranoside and novel methyl-l-idofuranoside systems.
-
synthesis and scalable conversion of l iduronamides to heparin related di and tetrasaccharides
Journal of Organic Chemistry, 2012Co-Authors: Steen U Hansen, Marek Barath, James Raftery, Gordon C Jayson, Gavin J Miller, Karl R Broberg, Egle Avizienyte, Madeleine Helliwell, John M GardinerAbstract:A diastereomerically pure cyanohydrin, preparable on kilogram scale, is efficiently converted in one step into a novel l-iduronamide. A new regioselective acylation of this iduronamide and a new mild amide hydrolysis method mediated by amyl nitrite enables short, scalable syntheses of an l-iduronate diacetate C-4 acceptor, and also l-iduronate C-4 acceptor Thioglycosides. Efficient conversions of these to a range of heparin-related gluco-ido disaccharide building blocks (various C-4 protection options) including efficient multigram access to key heparin-building block ido-Thioglycoside donors are described. A 1-OAc disaccharide is converted into a heparin-related tetrasaccharide, via divergence to both acceptor and donor disaccharides. X-ray and NMR data of the 1,2-diacetyl iduronate methyl ester and the analogous iduronamide show that while both adopt 1C4 conformations in solution, the iduronate ester adopts the 4C1 conformation in solid state. An X-ray structure is also reported for the novel, 4C1-confo...