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Synthesis of C ‐Glycosyl Amino Acid Building Blocks Suitable for the Solid‐Phase Synthesis of Multivalent Glycopeptide Mimics
Author(s) -
Reintjens Niels R. M.,
Koemans Tony S.,
Zilverschoon Nick,
Castelli Riccardo,
Cordfunke Robert A.,
Drijfhout Jan Wouter,
Meeuwenoord Nico J.,
Overkleeft Herman S.,
Filippov Dmitri V.,
Marel Gijsbert A.,
Codée Jeroen D. C.
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000587
Subject(s) - chemistry , glycopeptide , glycosyl donor , glycosyl , rhamnose , solid phase synthesis , combinatorial chemistry , stereochemistry , glycosidic bond , glycoside , organic chemistry , galactose , peptide , biochemistry , enzyme , antibiotics
Five C ‐glycosyl functionalized lysine building blocks, featuring C ‐glycosidic derivatives of α‐rhamnose, α‐mannose, α‐galactose, β‐galactose, and β ‐N ‐acetyl glucosamine have been designed and synthesized. These derivatives, equipped with acid‐labile protecting groups, are eminently suitable for solid‐phase synthesis of multivalent glycopeptides. The lysine building blocks were prepared from C ‐allyl glycosides that underwent a Grubbs cross‐metathesis with an acrylate, followed by a reduction of the C=C double bond in the resulting α,β‐unsaturated esters, and liberation of the carboxylate to allow condensation with a lysine side chain. The thus obtained C ‐glycosides, five in total, were applied in the solid‐phase peptide synthesis (SPPS) of three glycopeptides, showing the potential of the described building blocks in the assembly of well‐defined mimics of homo‐ and heteromultivalent glycopeptides and glycoclusters.