Use of fluorobenzoyl protective groups in synthesis of glycopeptides: beta-elimination of O-linked carbohydrates is suppressed.
Fluorobenzoyl groups have been investigated as alternatives to acetyl and benzoyl protective groups in carbohydrate and glycopeptide synthesis. D-Glucose and lactose were protected with different fluorobenzoyl groups and then converted into glycosyl bromides in high yields (>80% over two steps). Glycosylation of protected derivatives of serine with these donors gave 1,2-trans glycosides in good yields (approximately 60--70%) and excellent stereoselectivity without formation of ortho esters. The resulting glycosylated amino acid building blocks were then used in solid-phase synthesis of two model O-linked glycopeptides known to be unusually sensitive to beta-elimination on base-catalyzed deacylation. When either a 3-fluoro- or a 2,5-difluorobenzoyl group was used for protection of each of the two model glycopeptides the extent of beta-elimination decreased from 80% to 10% and from 50% to 0%, respectively, as compared to when using the ordinary benzoyl group. Fluorobenzoyl groups thus combine the advantages of the benzoyl group in formation of glycosidic bonds (i.e., high stereoselectivity and low levels of ortho ester formation) with the ease of removal characteristic of the acetyl group.
Sjölin
P
P
Organic Chemistry, Department of Chemistry, Umeå University, SE--901 87 Umeå, Sweden.
Kihlberg
J
J
D002241:Carbohydrates / Q000737:chemistry*; D002384:Catalysis; D002855:Chromatography, Thin Layer; D006020:Glycopeptides / Q000138:chemical synthesis*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet
D002241:Carbohydrates; D006020:Glycopeptides; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents