Open AccessSynthesis of a New Series of Sialylated Homo‐ and Heterovalent Glycoclusters by using Orthogonal Ligations
Author(s) -
Daskhan Gour Chand,
Pifferi Carlo,
Renaudet Olivier
Publication year - 2016
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201600062
Subject(s) - chemistry , glycoconjugate , combinatorial chemistry , glycosylation , sialic acid , thiol , neuraminic acid , conjugate , stereochemistry , cycloaddition , catalysis , organic chemistry , biochemistry , mathematical analysis , mathematics
The synthesis of heteroglycoclusters (hGCs) is being subjected to rising interest, owing to their potential applications in glycobiology. In this paper, we report an efficient and straightforward convergent protocol based on orthogonal chemoselective ligations to prepare structurally well‐defined cyclopeptide‐based homo‐ and heterovalent glycoconjugates displaying 5‐ N ‐acetyl‐neuraminic acid (Neu5Ac), galactose (Gal), and/or N ‐acetyl glucosamine (GlcNAc). We first used copper‐catalyzed azide–alkyne cycloaddition and/or thiol‐ene coupling to conjugate propargylated α‐sialic acid 3 , β‐GlcNAc thiol 5 , and β‐Gal thiol 6 onto cyclopeptide scaffolds 7 – 9 to prepare tetravalent homoglycoclusters ( 10 – 12 ) and hGCs ( 13 – 14 ) with 2:2 combinations of sugars. In addition, we have demonstrated that 1,2‐diethoxycyclobutene‐3,4‐dione can be used as a bivalent linker to prepare various octavalent hGCs ( 16 , 19 , and 20 ) in a controlled manner from these tetravalent structures.