Deacetylation of Nα-methylated glycopeptides reveals that aza-enolates provide protection against β-elimination of carbohydrates O-linked to serine

Design of Multivalent Galactoside Ligands and Their Binding to Hepatic Asialoglycoprotein Receptor

“…Here, 2-(2'-chloroethoxy) ethanol was chosen as the arm for this purpose. Firstly it reacted with peracetated galactose in the presence of BF 3 •Et 2 O, 15 after azidation and hydrogenation, the key intermediate 4 was obtained, which can be used directly in the next step without purification.…”

Use of Fluorobenzoyl Protective Groups in Synthesis of Glycopeptides: β-Elimination ofO-Linked Carbohydrates Is Suppressed

“…31 Glycopeptide 2 is exceptionally sensitive to β-elimination since the Nmethyl group attached to the glycosylated serine prevents formation of a protective aza-enolate on treatment with base. 31 Glycoproteins or glycopeptides found in nature do not contain galactose linked directly to serine, but the β-glucosyl serine linkage is found in proteins involved in blood coagulation and fibrinolysis. 32 Interestingly, attempts to remove O-benzoyl protective groups from synthetic glycopeptides having a β-glucosyl serine moiety were found to be accompanied by β-elimination.…”

“…(37) in which the glycosylated serine is N-methylated (Table 2). To allow this investigation N R -(fluoren-9-ylmethoxycarbonyl)-N R -methyl-L-serine pentafluorophenyl ester (Fmoc-NMe-Ser-OPfp) 31 was glycosylated with benzoylated bromosugar 13, 3-and 4-monofluorobenzoylated 15 and 16, as well as the 2,5-difluorobenzoylated 17. This gave building blocks 23-26 in 70-91% yields when silver triflate was used as promoter under the same conditions as described for synthesis of 18-22 (Table 1).…”

“…The reactions were allowed to progress until all of the protected glycopeptides had been consumed, after which the extent of β-elimination was determined by analytical reversedphase HPLC. Deprotection of the benzoylated 27 resulted in predominant β-elimination (∼80%) to give 31 31 (Table 2), the formation of which was reduced to ∼40% for 4-fluorobenzoylated 29. β-Elimination was further reduced for the 3-fluorobenzoylated 28 (∼20%), whereas the 2,5-difluorobenzoylated 30 gave an even better result (∼10% of 31). Thus, protection of the very base-labile glycopeptide 3 with either of the latter two fluorobenzoyl protective groups allowed the levels of β-elimination during deprotection to be decreased substantially, as compared to when using benzoyl protection.…”

“Polar patch” proteases as glycopeptiligases

“…Acetate protection of the glycosyl donor allowed absolute stereocontrol giving anomerically pure b-O-glycoside. The sugar-serine linkage is sensitive to b-elimination in basic environments 16 and this can cause difficulties in the removal of base-cleavable protecting { Electronic supplementary information (ESI) available: experimental details. See http://www.rsc.org/suppdata/cc/b4/b412030b/ *ben.davis@chem.ox.ac.uk groups.…”