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1‐Picolinyl‐5‐azido Thiosialosides: Versatile Donors for the Stereoselective Construction of Sialyl Linkages
Author(s) -
Chen Jian,
Hansen Thomas,
Zhang QingJu,
Liu DeYong,
Sun Yao,
Yan Hao,
Codée Jeroen D. C.,
Schmidt Richard R.,
Sun JianSong
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201909177
Subject(s) - stereoselectivity , chemistry , sialic acid , glycan , glycosylation , combinatorial chemistry , stereochemistry , substrate (aquarium) , protecting group , organic chemistry , catalysis , glycoprotein , biochemistry , oceanography , alkyl , geology
Abstract With the picolinyl (Pic) group as a C‐1 located directing group and N 3 as versatile precursor for C5‐NH 2 , a novel 1‐Pic‐5‐N 3 thiosialyl donor was designed and synthesized, based on which a new sialylation protocol was established. In comparison to conventional sialylation methods, the new protocol exhibited obvious advantages, including excellent α‐stereoselectivity in the absence of a solvent effect, broad substrate scope encompassing the challenging sialyl 8‐ and 9‐hydroxy groups of sialic acid acceptors, flexibility in sialoside derivative synthesis, high temperature tolerance and easy scalability. In particular, the applicability to the synthesis of complex and bioactive N ‐glycan antennae when combined with the MPEP glycosylation protocol via the “latent‐active” strategy has been shown. Mechanistically, the excellent α‐stereoselectivity of the novel sialylation protocol could be attributed to the dramatic electron‐withdrawing effect of the protonated Pic groups, which was supported by control reactions and DFT calculations.