1‐Picolinyl‐5‐azido Thiosialosides: Versatile Donors for the Stereoselective Construction of Sialyl Linkages. (4th 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. Volume 131:Number 47(2019)
• Page Start: 17156
• Page End: 17164
• Publication Date: 2019-10-04
• Subjects: Dirigierende Gruppen -- Glykosylierungen -- Glykan-Antennen -- Sialoside -- Stereoselektive Sialylierung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201909177
• Languages: English
• ISSNs: 0044-8249

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 : Zuckerbausteine : Mit 1‐Picolinyl‐5‐azidothiosialosid als Donor wurde ein robustes Sialylierungsprotokoll etabliert, das einen breiten Substratbereich, gute bis ausgezeichnete chemische Ausbeuten, eine ausgezeichnete α‐Stereoselektivität, eine flexible Synthese von Sialosiden, die in komplexen Sialosidsynthesen eingesetzt werden kann, sowie eine hohe Temperaturtoleranz und einfache Skalierbarkeit aufweist.