1‐Picolinyl‐5‐azido Thiosialosides: Versatile Donors for the Stereoselective Construction of Sialyl Linkages. Issue 47 (7th October 2019)

• Record Type: Journal Article
• Authors: Chen, Jian; Hansen, Thomas; Zhang, Qing‐Ju; Liu, De‐Yong; Sun, Yao; Yan, Hao; Codée, Jeroen D. C.; Schmidt, Richard R.; Sun, Jian‐Song
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 47(2019)
• Page Start: 17000
• Page End: 17008
• Publication Date: 2019-10-07
• Subjects: directing groups -- glycan antennae -- glycosylation -- sialoside -- stereoselective sialylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201909177
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: With the picolinyl (Pic) group as a C‐1 located directing group and N3 as versatile precursor for C5‐NH2, a novel 1‐Pic‐5‐N3 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. Abstract : Sugar building blocks : With 1‐Picolinyl‐5‐azido thiosialoside as donor, a robust sialylation was developed that is applicable to the flexible synthesis of complex sialosides and shows broad substrate scope, good to excellent chemical yield, excellent α‐stereoselectivity, high temperature tolerance, and easy scalability.