Chemical synthesis of some mono- and digalactosyl O-glycopeptides

Lacombe, Jean‐Michel; Pavia, A. A.

doi:10.1021/jo00163a027

Cited by 49 publications

(9 citation statements)

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“…Usually, their synthesis results i n low yields or involves circuitous/ cumbersome procedures, thus leaving margin for improvements in terms of stereoselectivity, efficiency and number of steps involved. Generally, t h e complications i n glycosylated amino acid synthesis are often caused by both acid lability of the glycosidic bond and the base sensitivity of the 0-serinyl and 0-threoninyl glycosides (35)(36)(37)(38)(39)(40). In addition, sequential glycosylation of serine and threonine for Fmoc-based glycopeptide synthesis involves a complex manipulation of the selectivities of base-sensitive protecting groups.…”

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confidence: 99%

“…However, glycosylation of the typical Fmoc-protected serine or threonine derivatives usually suffers in yield because of the poor reactivity in frequently used Koenigs-Knorr-type reactions. To overcome this poor reactivity, harsh reaction conditions are essential to trigger the 0-glycosylation which usually suppresses the yield as well as the anomer selectivity (35)(36)(37)(38)(39)(40). In view of these difficulties, we have devised a simple and efficient method to produce 0-glycosylated amino acid building blocks in good yields.…”

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confidence: 99%

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A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete ¹HNMR assignments and their application in solid‐phase glycopeptide synthesis

Satyanarayana

Gururaja

Naganagowda

et al. 1998

The Journal of Peptide Research

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A facile strategy for the stereoselective synthesis of suitably protected O‐glycosylated amino acid building blocks, namely, Nα‐Fmoc‐Ser‐[Ac4‐β‐d‐Gal‐(1‐3)‐Ac2α or β‐d‐GalN3]‐OPfp and Nα‐Fmoc‐Thr‐[Ac4‐β‐d‐Gal‐(1‐3)‐Ac2‐α or β‐d‐GalN3]‐OPfp is described. What is new and novel in this report is that Koenigs‐Knorr type glycosylation of an aglycon serine/threonine derivative (i.e. Nα‐Fmoc‐Ser‐OPfp or Nα‐Fmoc‐Thr‐OPfp) with protected β‐d‐Gal(1‐3)‐d‐GalN3 synthon mediated by silver salts resulted in only α‐and/or β‐isomers in excellent yields under two different reaction conditions. The subtle differences in stereoselectivity were demonstrated clearly when glycosylation was carried out using only AgClO4 at ‐40°C which afforded α‐isomer in a quantitative yield (α:β= 5:1). On the other hand, the β‐isomer was formed exclusively when the reaction was performed in the presence of Ag2CO3AgClO4 at room temperature. A complete assignment of 1H resonances to individual sugar ring protons and the characteristic anomeric α‐1H and β‐1H in Ac4Galβ(1‐3)Ac2GalN3α and/or β linked to Ser/Thr building blocks was accomplished unequivocally by two‐dimensional double‐quantum filtered correlated spectroscopy and nuclear Overhauser enhancement and exchange spectroscopy NMR experiments. An unambiguous structural characterization and documentation of chemical shifts, including the coupling constants for all the protons of the aforementioned a‐ and p‐isomers of the O‐glycosylated amino acid building blocks carrying protected β‐d‐Gal(1‐3)‐d‐GalN3, could serve as a template in elucidating the three‐dimensional structure of glycoproteins. The synthetic utility of the building blocks and versatility of the strategy was exemplified in the construction of human salivary mucin (MUC7)‐derived, O‐linked glycopeptides with varied degrees of glycosylation by solid‐phase Fmoc chemistry. Fmoc/tert‐butyl‐based protecting groups were used for the peptidic

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confidence: 99%

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confidence: 99%

A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete ¹HNMR assignments and their application in solid‐phase glycopeptide synthesis

Satyanarayana

Gururaja

Naganagowda

et al. 1998

The Journal of Peptide Research

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“…The chemical synthesis of 0-glycopeptides by glycosylation of a preformed peptide containing hydroxyaminoacids was shown to be less practical than a stepwise peptide coupling strategy using appropriate U-glycosylaminoacids (15). Furthermore, since the NH,-terminal glycopeptide of glycophorin AM possesses both unglycosylated and glycosylated serine and threonine, the latter route was preferred.…”

Section: Resultsmentioning

confidence: 99%

“…L-threonyl-glycine t-butyl ester (1 5). 15 was reacted with pure 8a to give the desired diglycosylated tripeptide I6 with 80% yield. Removal of the Fmoc groups was accomplished as before and compound 17 acylated with the p-nitrophenyl ester 9.…”

Section: Resultsmentioning

confidence: 99%

Blood group antigens: synthesis of TN glycopeptide related to human glycophorin AM

Ferrari

Pavia

2009

International Journal of Peptide and Protein Research

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Three 2‐acetamido‐2‐deoxy‐α‐d‐galactopyranose residues attached to Ser2, Thr3 Thr4 of the amino‐terminal portion of glycophorin AM are responsible for the so‐called TN blood group specificity. In a continuation of earlier work, this report describes the first chemical synthesis of the triglycosylated pentapeptide H2N‐Ser1‐Se*r2‐Th*r3‐Th*r4‐Gly5‐OH, in which (*) represents the 2‐acetamido‐2‐deoxy‐α‐d‐galactopyranosyl residue. This compound constitutes the G1‐G5 sequence of the amino‐terminal portion of human glycophorin AM, the main erythrocyte membrane glycoprotein. The above compound was obtained by a stepwise peptide coupling strategy alternatively using aminoacids and adequately protected and/or activated O ‐glycosyl‐aminoacids. Since the desired sequence possesses both unglycosylated and glycosylated serine this route was preferred to that in which the glycosylation is carried out on the preformed pentapeptide H2N‐Ser‐Ser‐Thr‐Thr‐Gly‐OH. Carbohydrate residues were introduced into the sequence as 2‐azido‐2‐deoxy‐α‐d‐galactopyranosyl‐l‐serine and l‐threonine derivatives. The azido functions were further converted into the corresponding acetamido groups by treatment of the final triglyco‐pentapeptide with sodium borohydride in the presence of nickel chloride followed by acetylation.

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“…This was also a promising result as it demonstrated the feasibility of utilizing our procedure in the synthesis of N-linked glycopeptide mimetics. [30] Since it has been demonstrated during the synthesis of Oglycopeptides that the hydroxyl group at the C-terminus has a much lower reactivity [31] than the hydroxyl group at the Nterminus, we thought it was important to examine the reactivity of a bromo group at the C-terminus. For this purpose, dipeptide 4 was treated with thiol 27 under the above described conditions, and interestingly, the a-thioglycoside 34 was produced in 83 % yield.…”

Section: Synthesis Of 1-thio Sugarsmentioning

confidence: 99%

Efficient Synthesis of S‐Linked Glycopeptides in Aqueous Solution by a Convergent Strategy

Zhu

Schmidt

2004

Chemistry A European J

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In naturally occurring glycopeptides and glycoproteins the glycan residues generally possess N- and O-linkages to the peptide backbone. Here we report the synthesis of the corresponding S-linked glycopeptides by a convergent strategy to provide compounds which should be quite stable to glycosidases. To this end, peptides that contain beta-bromoalanine and gamma-bromohomoalanine were generated either directly by bromination of serine and homoserine residues, respectively, or by standard ligation of the corresponding amino acids. 1-Thiosugars of O-acetyl protected GalNAc, GlcNAc, and lactose were prepared by known procedures. Reaction of the thiosugars with these peptides in an ethyl acetate/water two-phase system, which contained TBAHS and NaHCO(3), or in a one-phase system that consists of DMF/water and which contains NaHCO(3), led to the desired S-linked glycopeptides cleanly and in almost quantitative yield. This reaction also worked well for O-unprotected 1-thiosugars.

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Chemical synthesis of some mono- and digalactosyl O-glycopeptides

Cited by 49 publications

References 6 publications

A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete ¹HNMR assignments and their application in solid‐phase glycopeptide synthesis

A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete ¹HNMR assignments and their application in solid‐phase glycopeptide synthesis

Blood group antigens: synthesis of TN glycopeptide related to human glycophorin AM

Efficient Synthesis of S‐Linked Glycopeptides in Aqueous Solution by a Convergent Strategy

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Chemical synthesis of some mono- and digalactosyl O-glycopeptides

Cited by 49 publications

References 6 publications

A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete 1HNMR assignments and their application in solid‐phase glycopeptide synthesis

A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete 1HNMR assignments and their application in solid‐phase glycopeptide synthesis

Blood group antigens: synthesis of TN glycopeptide related to human glycophorin AM

Efficient Synthesis of S‐Linked Glycopeptides in Aqueous Solution by a Convergent Strategy

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A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete ¹HNMR assignments and their application in solid‐phase glycopeptide synthesis

A concise methodology for the stereoselective synthesis of O‐glycosylated amino acid building blocks: complete ¹HNMR assignments and their application in solid‐phase glycopeptide synthesis