Bacterial glycoproteins and oligosaccharides contain several rare deoxy amino l-sugars which are virtually absent in the human cells. This structural difference between the bacterial and host cell surface glycans can be exploited for the development of carbohydrate based vaccines and target specific drugs. However, the unusual deoxy amino l-sugars present in the bacterial glycoconjugates are not available from natural sources. Thus, procurement of orthogonally protected rare l-sugar building blocks through efficient chemical synthesis is a crucial step toward the synthesis of structurally well-defined and homogeneous complex glycans. Herein, we report a general and expedient methodology to access a variety of unusual deoxy amino l-sugars starting from readily available l-rhamnose and l-fucose via highly regioselective, one-pot double serial and double parallel displacements of the corresponding 2,4-bistriflates using azide and nitrite anions as nucleophiles. Alternatively, regioselective monotriflation at O2, O3, and O4 of l-rhamnose/l-fucose allowed selective inversions at respective positions leading to diverse rare sugars. The orthogonally protected deoxy amino l-sugar building blocks could be stereoselectively assembled to obtain biologically relevant bacterial O-glycans, as exemplified by the first total synthesis of the amino linker-attached, conjugation-ready tetrasaccharide of O-PS of Yersinia enterocolitica O:50 strain 3229 and the trisaccharide of Pseudomonas chlororaphis subsp. aureofaciens strain M71.
trisaccharide, Pseudomonas, glycoconjugates, vaccines, L-rhamnose, L-fucose, Yersinia enterocolitica, chemical synthesis, O-glycans
NCBI PubMed ID: 27002789Publication DOI: 10.1021/jacs.6b01823Journal NLM ID: 7503056Publisher: American Chemical Society
Correspondence: suvarn@chem.iitb.ac.in
Institutions: Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai 400076, India
Methods: 13C NMR, 1H NMR, TLC, GLC, chemical synthesis, chemical methods, MS, glycosylation
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