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Solid‐Phase Oligosaccharide Synthesis of a Small Library of N‐Glycans
Author(s) -
Jonke Simon,
Liu Kegang,
Schmidt Richard R.
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200500707
Subject(s) - chemistry , glycan , glycosylation , linker , oligosaccharide , solid phase synthesis , stereochemistry , glucosamine , residue (chemistry) , mannose , cleavage (geology) , glycosyl , acetylation , combinatorial chemistry , organic chemistry , peptide , biochemistry , glycoprotein , geotechnical engineering , fracture (geology) , computer science , gene , engineering , operating system
Solid‐phase oligosaccharide synthesis is based on a hydroxymethylbenzyl benzoate spacer linker which is connected to the Merrifield resin ( 1 P ). Glycosylation was performed with O‐glycosyl trichloroacetimidates of glucosamine, mannose, and galactose permitting chain extension ( 2 e , 5 e ), branching ( 4 b , 7 b , 8 b ), and chain termination ( 3 t , 6 t , 9 t ) with the use of O‐benzyl, O‐benzoyl, and N‐dimethylmaleoyl as permanent and O‐fluorenylmethoxycarbonyl (Fmoc) and O‐phenoxyacetyl (PA) as temporary protecting groups. The steps required on solid phase are i) glycosylation under TMSOTf catalysis, ii) selective cleavage of the temporary protecting groups, Fmoc with NEt 3 and PA with 0.5 equivalents of NaOMe in CH 2 Cl 2 /MeOH, and iii) product cleavage from the resin with 4.0 equivalents of NaOMe in CH 2 Cl 2 /MeOH and following O‐acetylation for convenient product isolation. Thus a highly successful synthesis of a small library of seventeen N‐glycan structures was made possible comprising the N‐glycan pentasaccharide core structure 53 and two further chain extended hexa‐ and heptasaccharide N‐glycans with a glucosamine or a lactosamine residue, respectively, which is attached to one of the mannose residues of the core structure ( 56 and 59 ).