Competitive formation of peracetylated α- l -arabinopyranosides and β- l -arabinopyranose 1,2-(alkyl orthoacetates) in Koenigs-Knorr condensations

Magnus, Volker; Vikić-Topić, Drazˇen; Iskrić, Sonja; Kveder, S.

doi:10.1016/0008-6215(83)88188-9

Cited by 28 publications

(11 citation statements)

References 23 publications

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“…In one case kinetic evidence was presented to support this hypothesis . Acyl transfer was postulated as a side reaction of this rearrangement process . This work provides experimental results supplemented by some theoretical studies which give some ideas on how to minimize this side reaction.…”

Section: Introductionmentioning

confidence: 89%

Acyl Transfer as a Problematic Side Reaction in Polymer-Supported Oligosaccharide Synthesis

1999

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Under a wide variety of glycosylation conditions acyl transfer to the polymer support competed with glycoside formation, including the pivaloyl protecting group. As well as acyl transfer, many glycosylations also led to the formation of polymer-bound β-1,2-linked oligomers of the donor. Using ethyl 2,6-di-O-pivaloyl-3,4-O-isopropylidene-β-d-galactothiopyranoside as donor under promotion of N-iodosuccinimide/silver trifluoromethanesulfonate in the presence of 2-methyl-2-butene, an 82% yield of glycoside was obtained along with pivaloylated polymer. Subsequent work showed that increasing the steric bulk about the alcoholic acceptor in conjunction with this 2-O-pivaloyl-protected glycosyl donor completely suppresses this side reaction, giving a nearly quantitative yield of glycoside. This contraintuitive approach of decreasing the reactivity of both the donor and the acceptor to minimize a side reaction is rationalized by assuming that the barrier to acyl transfer is more sensitive to the protecting groups than that of glycosylation. These developments led to a polymer-supported synthesis of the branch point trisaccharide of the group B type 1A Streptococcus capsular polysaccharide.

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Section: Introductionmentioning

confidence: 89%

Acyl Transfer as a Problematic Side Reaction in Polymer-Supported Oligosaccharide Synthesis

1999

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“…This is often done via reaction of an activated group (e.g., Br on a furthermore peracetylated sugar) at the anomeric center and is textbook oligosaccharide chemistry . Despite this, the yields of the initial glycosylations by sugar peracetates are frequently modest (30–50%) because of the formation of ortho esters in a side reaction that is common for glycosyl donors bearing an acetyl group at C-2 . To avoid such ortho ester formation, this acetyl group can be replaced by a sterically more demanding benzoyl or pivaloyl group.…”

Section: Gm1-based Dendrimersmentioning

confidence: 99%

Fighting Cholera One-on-One: The Development and Efficacy of Multivalent Cholera-Toxin-Binding Molecules

Zuilhof

2016

Acc. Chem. Res.

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A series of diseases, ranging from cholera via travelers' diarrhea to hamburger disease, are caused by bacterially produced toxic proteins. In particular, a toxic protein unit is brought into the host cell upon binding to specific membrane-bound oligosaccharides on the host cell membrane. For example, the protein that causes cholera, cholera toxin (CT), has five identical, symmetrically placed binding pockets (B proteins), on top of which the toxic A protein resides. A promising strategy to counteract the devastating biological effects of this AB5 protein involves the development of inhibitors that can act as mimics of membrane-bound GM1 molecules, i.e., that can bind CT strongly and selectively. To reach this goal, two features are essential: First of all, the inhibitor should display oligosaccharides that resemble as much as possible the naturally occurring cell-surface pentasaccharide onto which CT normally binds, the so-called GM1 sugar (the oligosaccharide part of which is then labeled GM1os). Second, the inhibitor should be able to bind CT via multivalent interactions so as to bind CT as strongly as possible to allow for a real competition with the cell-membrane-bound GM1 molecules. In this Account, we present elements of the path that leads to strong CT inhibition by outlining the roles of multivalency and the development and use of GM1 mimics. First, multivalency effects were investigated using "sugar-coated" platforms, ranging from dendritic structures with up to eight oligosaccharides to platforms that mimicked the fivefold symmetry of CT itself. The latter goal was reached either via synthetic scaffolds like corannulene or calix[5]arene or via the development of a neolectin CT mimic that itself carries five GM1os groups. Second, the effect of the nature of the oligosaccharide appended to this platform was investigated via the use of oligosaccharides of increasing complexity, from galactose and lactose to the tetrasaccharide GM2os and eventually to GM1os itself. The combination of these threads gives rise to a series of inhibitors that can strongly bind CT, with IC50 values below 100 pM, and in some cases can even bind one-on-one.

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“…Treatment of hemiacetal 5, [26] prepared by hydrolysis of the glycosyl bromide 4, with 2-naphthol (diethyl azodicarboxylate, triphenylphosphane, 0°C, tetrahydrofuran) afforded the desired aryl glycoside 12 in 39% yield. While this yield was higher than the yield of 12 prepared under KönigsϪKnorr conditions (9%), the reaction failed in DMF, the solvent of choice for the corresponding reaction with ellipticines 2 and 3.…”

Section: Preparation Of O-aryl Glycosidesmentioning

confidence: 99%

“…After 4 h, the insoluble silver salts were removed by filtration (0.45 µm Millipore filter) and the solvent removed to give hemiacetal 5 [26] …”

Section: 34-tri-o-acetyl-l-arabinose (5)mentioning

confidence: 99%

Carbohydrate Derivatives of the Antitumour Alkaloid 9-Hydroxyellipticine

et al. 2003

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The synthesis of L-arabinosyl derivatives of 2-naphthol and the quaternised ellipticines Celiptium (2) and Ellipravin (3) is reported. Naphth-2-yl 2Ј,3Ј,4Ј-tri-O-acetyl-α-L-arabinopyranoside was prepared under Königs−Knorr and Mitsunobu conditions in nonpolar aprotic solvents and using 2,3,4-tri-O-acetyl-L-arabinopyranosyl fluoride as the glycosyl donor. These conditions were not applicable to the corresponding glycosidation reactions with the quaternised ellipticines 2 and 3 which are soluble only in polar solvents. Formation of the 9-(α-L-arabinopyranosyl)ellipticine derivatives 13 and 14 was achieved by using 2,3,4-tri-O-acetyl-L-arabinopyranosyl bromide in the presence of sodium methoxide in methanol. Improved yields were obtained under the same conditions [a]

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Competitive formation of peracetylated α- l -arabinopyranosides and β- l -arabinopyranose 1,2-(alkyl orthoacetates) in Koenigs-Knorr condensations

Cited by 28 publications

References 23 publications

Acyl Transfer as a Problematic Side Reaction in Polymer-Supported Oligosaccharide Synthesis

Acyl Transfer as a Problematic Side Reaction in Polymer-Supported Oligosaccharide Synthesis

Fighting Cholera One-on-One: The Development and Efficacy of Multivalent Cholera-Toxin-Binding Molecules

Carbohydrate Derivatives of the Antitumour Alkaloid 9-Hydroxyellipticine

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