Solid-phase synthesis of a glycosylated hexapeptide of human sialophorin, using the trichloroacetimidate method

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• 作者：Rademann ; Jö ; rg ; Schmidt ; Richard R.
• 关键词：O-Glycopeptides ; Glycosyl trichloroacetimidates ; Peptide synthesis ; solid phase ; N-Fmoc protection ; Pentafluorophenyl esters
• 刊名：Carbohydrate Research
• 出版年：1995
• 出版时间：April 19, 1995
• 年：1995
• 卷：269
• 期：2
• 页码：217-225
• 全文大小：518 K

文摘

A hexapeptide containing a β-d-Galp-(1 → 3)-α-d-GalpNAc-(1 → O)-l-threonine unit was synthesized using glycosylated pentafluorophenyl esters in an Fmoc-based strategy. In all of the glycosylation reactions, trichloroacetimidates were successfully employed. The disaccharide moiety was prepared from tetra-O-acetyl-α-d-galactopyranosyl trichloroacetimidate and tert-butyldimethylsilyl 2-azido-6-O-benzoyl-2-deoxy-β-e-galactopyranoside with boron trifluoride etherate as a catalyst. The glycosylated active esters were obtained in the reaction of α and β 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1 → 3)-4-O-acetyl-2-azido-6-O-benzoyl-2-deoxy-d-galactopyranosyl trichloroacetimidates with Fmoc-protected pentafluorophenyl esters of l-serine and l-threonine in the presence of trimethylsilyl trifluoromethanesulfonate as Lewis acid. The glycosylated pentafluorophenyl ester of l-threonine was transformed into glycopeptides via a solid-phase synthesis. Azide reduction and N-acetylation were performed on the solid phase with a thioacetic acid-pyridine mixture. The glycopeptide was then cleaved from the resin with strong acid, also removing the acid-labile protecting groups of the peptide chain. Finally, the acyl groups used for sugar protection were cleaved with sodium methoxide, affording the completely deprotectedN -acetyl-l-leucyl-l-glutamyl-O-[β-d-galactopyranosyl-(1 → 3)-2-acetamido-2-deoxy-α-d-galactopyranosyl]-l-threonyl-l-seryl-l-threonyl-glycinamide (1) in high purity.