Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in vivo has been a challenging task. In an effort to overcome this long-standing problem, we selected interferon-β and examined its synthesis. The 166 residue polypeptide chain of interferon-β was prepared by covalent condensation of two synthetic peptide segments and a glycosylated synthetic peptide bearing a complex-type glycan of biological origin. The peptides were covalently condensed by native chemical ligation. Selective desulfurization followed by deprotection of the two Cys(Acm) residues gave the target full-length polypeptide chain of interferon-β bearing either a complex-type sialyl biantennary oligosaccharide or its asialo form. Subsequent folding with concomitant formation of the native disulfide bond afforded correctly folded homogeneous glycosyl-interferon-β. The chemically synthesized sialyl interferon-β exhibited potent antitumor activity in vivo.

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Partial sialyl transfer reaction by alpha-(2,3)-sialyltransferase toward (Gal-beta-1,4-GlcNAc-beta-1,2-Man-alpha-1,6/1,3-)(2)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-asparagine-Fmoc 1 was examined to obtain mono-alpha-(2,3)-sialyloligosaccharides and then branch-specific exo-glycosidase digestion (beta-D-galactosidase, N -acetyl-beta-D-glucosaminidase and alpha-D-mannosidase) toward the asialo-branch was performed to obtain diverse asparagine-linked complex type alpha-(2,3)-sialyloligosaccharides. In addition, two kinds of disialyloligosaccharides in which the sialyl linkage was a mixture of alpha-(2,3)- and alpha-(2,6)-types were also specifically prepared by an additional alpha-(2,6)-sialyltransferase reaction toward mono-alpha-(2,3)-sialyloligosaccharides thus obtained.

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Abstract-Oxidative carbon-carbon bond cleavage of N-alkoxycarbonylated cyclic amines was accomplished by NaNO 2 in TFA to afford ω-amino carboxylic acid in high yield. Optically active 3-hydroxypiperidine derivatives and 3-pipecolinate, were converted to enantiomerically pure (R)-4-amino-3-hydroxybutanoic acid (GABOB) and (S)-2-pyrrolidone-4-carboxylate, respectively.It is well known that trifluoroacetic acid (TFA) acts as an efficient medium for oxidation of hydrocarbons.1 Recently, we found that efficient oxidation of adamantanes to 1-adamantanols was catalyzed by sodium nitrite (NaNO 2 ) under oxygen atmosphere in TFA. 2 In addition, 2 equiv of NaNO 2 in TFA 3 oxidized acyclic and cyclic secondary alcohols to the corresponding ketones and α,ω-dicarboxylic acid, respectively. 4 In the latter case, oxidative cleavage of cyclic secondary alcohols occurred between the α-carbon and the β-carbon. We report herein that this oxidizing agent works well as demonstrated by a unique reaction of N-alkoxycarbonylated cyclic amines 1 which reacted with NaNO 2 to afford the ring-opened products 2 5 and its application to preparation of optically active compounds 3e and 4 (Eq. 1). 2. The oxidation of 1a (1 mmol) was carried out in TFA (5 mL) containing NaNO 2 (2 mmol) and H 2 O (10 mmol) under aerobic condition. The oxidation smoothly proceededKey words: carbon-carbon cleavage; cyclic amines; trifluoroacetic acid; sodium nirite; ω-amino acid * Corresponding author, Tel +81-95-819-2429, Fax +81-95-819-2476 at 0 o C to rt for 3 h to afford an oxidative ring-opened product 2a in 94% yield. The oxidative cleavages of N-protected pyrrolidines 1b-d and piperidines 1e-i with NaNO 2 in TFA were examined to clarify generality of substrates (Eq. 3). The results are summarized in Table 1.