Total synthesis of sialylated glycans related to avian and human influenza virus infection.
Human and avian influenza type A viruses bind sialylated pentasaccharides. Herein, the total synthesis of four of these glycans is reported. Efficient sialylations relied on two N-Troc-protected (Troc = 2,2,2-trichloroethoxycarbonyl) sialic acid building blocks. The first, a thiophenyl glycoside, readily produced the sialyl-alpha(2-6)galactose disaccharide. Combination of the second building block, a novel glycosyl phosphite, and a benzylidene-protected galactoside produced the best results for the formation of the sialyl-alpha(2-3)galactose. Two common trisaccharides were assembled by the introduction of glucose, galactose, and glucosamine building blocks followed by selective deprotection. Two sets of pentasaccharides were obtained by the union of two sialylgalactose N-phenyl trifluoroacetimidate building blocks with the two trisaccharides above. Global deprotection furnished the desired pentasaccharides. The products of these total syntheses are currently employed on the surface of carbohydrate microarrays to detect and type different strains of the influenza virus.
Hanashima
Shinya
S
Laboratory for Organic Chemistry, Swiss Federal Institute of Technology ETH Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.
Seeberger
Peter H
PH
D000818:Animals; D001717:Birds; D006801:Humans; D005585:Influenza in Birds / Q000378:metabolism*; D007251:Influenza, Human / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D011134:Polysaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid