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A Diazido Mannose Analogue as a Chemoenzymatic Synthon for Synthesizing Di‐ N ‐acetyllegionaminic Acid‐Containing Glycosides
Author(s) -
Santra Abhishek,
Xiao An,
Yu Hai,
Li Wanqing,
Li Yanhong,
Ngo Linh,
McArthur John B.,
Chen Xi
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201712022
Subject(s) - synthon , chemistry , sialic acid , monosaccharide , glycoside , yield (engineering) , mannose , stereochemistry , glycan , chemical synthesis , combinatorial chemistry , organic chemistry , biochemistry , in vitro , glycoprotein , materials science , metallurgy
Abstract A chemoenzymatic synthon was designed to expand the scope of the chemoenzymatic synthesis of carbohydrates. The synthon was enzymatically converted into carbohydrate analogues, which were readily derivatized chemically to produce the desired targets. The strategy is demonstrated for the synthesis of glycosides containing 7,9‐di‐ N ‐acetyllegionaminic acid (Leg5,7Ac 2 ), a bacterial nonulosonic acid (NulO) analogue of sialic acid. A versatile library of α2‐3/6‐linked Leg5,7Ac 2 ‐glycosides was built by using chemically synthesized 2,4‐diazido‐2,4,6‐trideoxymannose as a chemoenzymatic synthon for highly efficient one‐pot multienzyme (OPME) sialylation followed by downstream chemical conversion of the azido groups into acetamido groups. The syntheses required 10 steps from commercially available d ‐fucose and had an overall yield of 34–52 %, thus representing a significant improvement over previous methods. Free Leg5,7Ac 2 monosaccharide was also synthesized by a sialic acid aldolase‐catalyzed reaction.