Low‐Concentration 1,2‐<i>trans</i> β‐Selective Glycosylation Strategy and Its Applications in Oligosaccharide Synthesis

Chao, Chin-Sheng; Li, Chenwei; Chen, Minchun; Chang, Shih-Sheng; Mong, Kwok-Kong Tony

doi:10.1002/chem.200901119

Cited by 65 publications

(35 citation statements)

References 117 publications

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“…Flash column chromatography was performed on silica gel (E. Merck, Si-60, particle size 0.063 to 0.200 mm). NMR spectra were recorded with Bruker DRX 300, Varian Unity 300 (300 MHz for General LCG procedure for the disaccharides 8-13: [10] A mixture of the thioglycoside 1, 2, 3, 4, 5, or 6 (0.23 mmol, 1.2 equiv), the galactosyl acceptor 7 (0.19 mmol, 1.0 equiv), and molecule sieves (flame-dried, AW300) in CH 2 Cl 2 /CH 3 CN/EtCN (1:2:1) was cooled to À70 8C and stirred under N 2 for ca. 30 min (exact amounts of reagents and specific reaction conditions are detailed in Table S1 in the Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

“…[9] In 2009 we reported a low-concentration b-selective glycosylation method (LCG) that enables the formation of 1,2-trans b-glycosidic bonds in CH 2 Cl 2 and nitrile solvent mixtures (CH 2 Cl 2 /RCN) and the C-2 ester-participating function is thus not required. [10] In a carbohydrate context, the b-selectivity in glycosylation selectivity in a nitrile solvent is usually attributed to the formation of a-glycosyl nitrilium interKeywords: arabinans · glycosylation · neighboring-group effects · nitrile solvents · oligosaccharides Abstract: Ether-protecting functions at C-2 hydroxy groups have been found to play participating roles in glycosylations when the reactions are conducted in nitrile solvent mixtures. The participation mechanism is based on intramolecular interaction between the lone electron pair of the oxygen atom of the C-2 ether function and the nitrile molecule when they are positioned in a cis configuration.…”

Section: Introductionmentioning

confidence: 99%

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Neighboring‐Group Participation by C‐2 Ether Functions in Glycosylations Directed by Nitrile Solvents

Chao

Lin

Mulani

et al. 2011

Chemistry A European J

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Ether-protecting functions at C-2 hydroxy groups have been found to play participating roles in glycosylations when the reactions are conducted in nitrile solvent mixtures. The participation mechanism is based on intramolecular interaction between the lone electron pair of the oxygen atom of the C-2 ether function and the nitrile molecule when they are positioned in a cis configuration. A 1,2-cis glycosyl oxazolinium intermediate is formed. This participation, in conjunction with the anomeric effect of the glycosyl donor, confers high 1,2-trans selectivities on glycosylations. Further application of this concept has led to efficient preparations of α-(1→5)-arabinan oligomers.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neighboring‐Group Participation by C‐2 Ether Functions in Glycosylations Directed by Nitrile Solvents

Chao

Lin

Mulani

et al. 2011

Chemistry A European J

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“…Using aCH 2 Cl 2 / Et 2 Osolvent system at À40 8 8C, a70%yield of tetrasaccharide T3 was obtained as a3 :1 a/b-mixture.T oi mprove the aselectivity higher temperatures were investigated, as suggested in the literature. [23,24] At emperature of À10 8 8C afforded T3 in similar yield (66 %) but with complete astereoselectivity.T hese conditions were then utilized in glycosylation reactions to get intermediate,a ppropriately protected tetra-(T1, T5, and T7) and hexasaccharides (H1-H5) with good to excellent results (55-98 %y ields,3 :1 to > 15:1 a-selectivity,see Table S1). Only in one glycosylation, i.e., between donor D1 and acceptor D10 to prepare tetrasaccharide T9, was further optimization required.…”

Section: Angewandte Chemiementioning

confidence: 85%

A Hexasaccharide Containing Rare 2‐O‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

et al. 2017

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Glycosaminoglycan (GAG) sequences that selectively target heparin cofactor II (HCII), akey serpin present in human plasma, remain unknown. Using ac omputational strategy on alibrary of 46 656 heparan sulfate hexasaccharides we identified ar are sequence consisting of consecutive glucuronic acid 2-O-sulfate residues as selectively targeting HCII. This and four other unique hexasaccharides were chemically synthesized. The designed sequence was found to activate HCII ca. 250-fold, while leaving aside antithrombin, ac losely related serpin, essentially unactivated. This group of rare designed hexasaccharides will help understand HCII function. More importantly,our results show for the first time that rigorous use of computational techniques can lead to discovery of unique GAGsequences that can selectively target GAG-binding protein(s), which may lead to chemical biology or drug discovery tools.Heparin cofactor II (HCII) is as erine protease inhibitor (serpin) that circulates in human plasma at high levels. Although it has been known to selectively inhibit thrombin for several decades, [1][2][3] its true physiologic function remains to be understood. [4] HCII is known to bind to glycosaminoglycans (GAGs) such as dermatan sulfate (DS) and heparan sulfate (HS), which help mediate its inhibition of thrombin. One of the key reasons for the inability to identify HCIIs biologic role is the lack of knowledge on the specificity of HCII-GAGi nteraction.HCII is an interesting serpin. It bears considerable similarity to antithrombin (AT), another plasma serpin that mediates the anticoagulant action of heparin and fondaparinux, [5,6] two clinically used drugs.A Tand HCII are homologous in primary,secondary and tertiary structure ( Figure S1 in the Supporting Information). Yet, whereas AT binds specifically to fondaparinux sequence in heparin, [7] HCII is considered to bind non-specifically to heparin and HS. Further,a lthough both serpins display at wo-step,i nducedfit, allosteric activation mechanism in inhibiting their target enzymes, [8][9][10] no HS oligosaccharide has been discovered to induce robust activation of HCII.Identifying GAGs equences that selectively target proteins is extremely challenging.Akey reason for this is their structural complexity.H S, ah ighly anionic polymer containing variably sulfated, acetylated and epimerized residues, presents enormous structural diversity that makes comprehensive analysis of all possible sequences difficult. Thus, identifying key "needles" in this haystack, especially with synthesis [11,12] or isolation of oligosaccharides from nature nearly impossible. [13] We had earlier developed ad ual-filter computational algorithm, called combinatorial virtual library screening (CVLS) strategy,torapidly sort HS sequences into "specific" and "non-specific" bins. [14,15] We wondered whether this tool could pinpoint HS sequences that preferentially activate HCII for inhibition of thrombin. Further, we posited that such asequence,ifany,would be different from the pentasaccharide seq...

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“…They rationalized this intriguing result by enhanced formation of nitrilium ion intermediates with low concentration of substrates (23).…”

Section: C-3 Glycosylation In Various Solvents Under Frozen Conditionsmentioning

confidence: 96%

Accelerated O-Glycosylation under Frozen Conditions and Its Application to the Synthesis of Complex Glycans

Ishiwata

Sakurai

Ito

2012

TIGG

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Enormous rate acceleration was observed when O-glycosylation was conducted in p-xylene below its freezing point, as determined by comparative studies under both frozen and unfrozen conditions. The mechanistic implications of stereoselectivity on glycosylation under frozen systems were also investigated. Examination of the effects of various factors, such as solvent, concentration, anomeric configuration and protective groups of the donor, revealed that the stereoselectivity was affected by concentration both in liquid and in frozen conditions. The rate acceleration in frozen solvent was caused by the highly concentrated environments found therein. The substrate concentration under frozen conditions was estimated to be about 50 times higher than that before freezing. This manuscript also summarizes the application of this technique to the synthesis of complex glycans as well as bioactive molecules.

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Low‐Concentration 1,2‐trans β‐Selective Glycosylation Strategy and Its Applications in Oligosaccharide Synthesis

Cited by 65 publications

References 117 publications

Neighboring‐Group Participation by C‐2 Ether Functions in Glycosylations Directed by Nitrile Solvents

Neighboring‐Group Participation by C‐2 Ether Functions in Glycosylations Directed by Nitrile Solvents

A Hexasaccharide Containing Rare 2‐O‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

Accelerated O-Glycosylation under Frozen Conditions and Its Application to the Synthesis of Complex Glycans

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