Solid-phase synthesis of core 3 and core 6 O-glycan-linked glycopeptides by benzyl-protection method

Nakahara, Yuko; Ozawa, Chinatsu; Tanaka, Eriko; Ohtsuka, Kazuki; Takano, Yutaka; Hojo, Hironobu; Nakahara, Yoshiaki

doi:10.1016/j.tet.2006.12.087

Cited by 22 publications

(6 citation statements)

References 25 publications

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“…The trisaccharide was designed as the suitably protected form equipped with TBDPS group on the 1-position of the glucosamine and an allyl group on the 3-position of the galactose for divergent synthesis of the acceptor and the donor. In addition, the trichloroacetyl (TCA) group on the 2-position of the glucosamine and the benzyl groups were expected to ensure high stereoselectivity and high yield during the later glycosylation [4,[6][7][8][9][10][11][12][13]. We envisioned that the tetramer could be obtained by glycosylation promoted by a catalytic Lewis acid with haxasaccharyl acceptor and donor, which could be prepared from the hexasaccharide Le a dimer, and the hexasaccharide could be synthesized by coupling the acceptor and N-phenyl trichloroacetimidyl donor provided from the Le a trisaccharide common intermediate (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Efficient Synthesis of the Lewis A Tandem Repeat

et al. 2016

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Abstract:The convergent synthesis of the Lewis A (Le a ) tandem repeat is described. The Le a tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le a unit,was synthesized by stereoselective nitrile-assisted β-galactosylation with the phenyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-β-galactoside, and ether-assisted α-fucosylation with fucosyl (N-phenyl)trifluoroacetimidate. This common Le a unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Le a tandem repeat framework was achieved by 2-trichloroacetamido-assisted β-glycosylation and the (N-phenyl)trifluoroacetimidate method.

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Section: Resultsmentioning

confidence: 99%

Efficient Synthesis of the Lewis A Tandem Repeat

et al. 2016

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“…[14] Although syntheses of these specific core 3 & core 4-type methyl glycosides have not been previously reported, the synthesis of related core 3 & core 4 derivatives has been investigated by several groups using both chemical and chemoenzymatic approaches. [17][18][19][20][21][22][23][24] Prior syntheses have been primarily focused on generating glycosylated amino acid derivatives for solid-phase peptide synthesis of glycopep-tide mucin mimetics. An advantage of the methyl glycoside derivatives is that they are inherently more stable than glycopeptide derivatives, therefore facilitating the assembly of more complex glycan structures from purely chemical methods, as well as enabling more diverse and/or forceful reaction conditions to improve scalability.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Core 3 & Core 4‐Type Mucin Glycan Derivatives

Cori,

Hevey

2024

Helvetica Chimica Acta

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Recent studies have demonstrated the ability of mucin O‐glycans to attenuate virulence in diverse, cross‐kingdom pathogens, sparking interest in their development as a novel therapeutic approach against infection. Although their virulence attenuating activity is evident, mucin glycans obtained from native sources comprise mixtures of several hundred distinct structures, and therefore the specific active glycan epitopes and molecular mechanisms of virulence attenuation remain unclear. Individual mucin glycan structures cannot be purified from native sources and are not amenable to automated synthesis; therefore, to further investigate the phenomena of virulence attenuation we have been developing convergent and scalable methods (>30 mg per target glycan) to assemble a mucin O‐glycan library in sufficient scale and purity to facilitate biological studies. Previously we described a method to obtain core 1 & core 2‐type mucin glycan derivatives that have since been used to identify active epitopes in Candida albicans and Vibrio cholerae. In the current study, we describe the expansion of our glycan library to include core 3 & core 4‐type derivatives, increasing the structural diversity of our platform for biological evaluation.

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“…This method has been successfully used for the synthesis of various glycopeptides and glycoproteins. [5][6][7][8][9][10][11][12][13][14][15][16] The benzyl protection strategy for the carbohydrate moiety has several advantages over the more common acetyl protection strategy: (1) the benzyl-protected sugars usually retain higher reactivity during the glycosylation reactions, which is useful for the construction of complex sugar chains; (2) the benzyl groups are stable under the basic conditions used for the Fmoc-SPPS, which is free from side reactions, such as acyl migration from the carbohydrate to the terminal amino group of the growing peptide chain; and (3) the cleavage of the benzyl group does not require the alkaline conditions, such as NaOMe treatment, which have the potential danger of racemization of amino acid residues and β-elimination of the carbohydrate moiety. Instead, the complexity of this method is that a two-step deprotection is required at the end of the Fmoc-SPPS as follows: (1) TFA treatment to deprotect the peptide portion and (2) the Low-TfOH [17] treatment to deprotect the carbohydrate chain.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Fmoc-Thr Unit Carrying Core 1O-Linked Sugar With Acid-SensitiveO-Protecting Group and Its Application to the Synthesis of Glycosylated Peptide Thioester

Asahina

Fujimoto

Suzuki

et al. 2014

Journal of Carbohydrate Chemistry

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Y. Asahina et al.We newly designed and synthesized a 9-fluorenylmethoxycarbonyl (Fmoc)-threonine unit carrying the core 1 O-glycan, which is protected by the 4-methylbenzyl (MBn) group. This protection tactic enabled not only efficient assembly of glycoamino acid derivatives but also one-step deprotection by trifluoroacetic acid (TFA) after the Fmocsolid-phase peptide synthesis (SPPS). The usefulness of this unit was demonstrated by the Fmoc-SPPS of peptide thioester using the N-alkylcysteine (NAC)-assisted thioesterification method. The human interleukin-2 (1-27) sequence was assembled on the NAC resin and the obtained resin was treated with TFA containing cation scavengers to achieve one-step deprotection. The crude peptide was then thioesterified by reacting with an arylthiol to successfully obtain the desired peptide thioester carrying the core 1 O-glycan.

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Solid-phase synthesis of core 3 and core 6 O-glycan-linked glycopeptides by benzyl-protection method

Cited by 22 publications

References 25 publications

Efficient Synthesis of the Lewis A Tandem Repeat

Efficient Synthesis of the Lewis A Tandem Repeat

Total Synthesis of Core 3 & Core 4‐Type Mucin Glycan Derivatives

Synthesis of Fmoc-Thr Unit Carrying Core 1O-Linked Sugar With Acid-SensitiveO-Protecting Group and Its Application to the Synthesis of Glycosylated Peptide Thioester

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