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Central heteroaryl ring analogues belonging to a series of potent hydroxamate TACE inhibitors were synthesized. The TACE inhibitory activities of these compounds were evaluated by in vitro WBA and in silico molecular modeling studies using crystal structure of human TACE. Compound 14 showed very good in vitro inhibition, supported by the in silico docking studies.

A series of sialylated β- d -Gal-(1→3)-α- d -GalNAc-octyl containing oligosaccharides representative of those found on mucin type complex O -glycans were synthesized by a chemoenzymatic approach for use in the kinetic characterization of recently cloned polysialyltransferases. Enzymatic incorporation of N -acetylneuraminic acid (sialic acid) into the synthetic acceptors was accomplished by 2,3-( N ) and ( O )-sialyltransferases to give the target compounds 6 – 10 in a practical yield.

Starting from L-fucose, D-galactose and 2-amino-2-deoxy-D-galactose, methyl 2-acetamido-2-deoxy-β-D-galactopyranosyl-(1→4)-α-D-galactopyranoside and methyl 2-acetamido-2-deoxy-β-D-galactopyranosyl-(1→6)-[α-L-fucopyranosyl-(1→2)]-β-D-galactopyranoside, which are related to the repeating unit of E.coli O128, have been synthesized using NIS and TfOH as promoter.

Starting from D-galactose and L-fucose, four disaccharides, namely methyl β-L-fucopyranosyl-(1→2)-α-D-galactopyranoside, methyl α-L-fucopyranosyl-(1→2)-α-D-galactopyranoside, methyl α-L-fucopyranosyl-(1→2)-β-D-galactopyranoside and methyl β-L-fucopyranosyl-(1→2)-β-D-galactopyranoside related to the repeating units of E.coli O126 and O128 have been synthesized using NIS and TfOH as promoter.

Starting from D-galactose and L-fucose, four disaccharides, namely methyl β-L-fucopyranosyl-(1→2)-α-D-galactopyranoside, methyl α-L-fucopyranosyl-(1→2)-α-D-galactopyranoside, methyl α-L-fucopyranosyl-(1→2)-β-D-galactopyranoside and methyl β-L-fucopyranosyl-(1→2)-β-D-galactopyranoside related to the repeating units of E.coli O126 and O128 have been synthesized using NIS and TfOH as promoter.

The immunodominant part in the O-antigenic polysaccharide from Escherichia coli O128 was immunologically characterized by an enzyme-linked immunosorbent assay (ELISA). The antibody specificity was determined by the inhibitory effects of the methyl glycosides of constituent mono- and oligosaccharides synthesized related to the O-antigenic polysaccharide from E. coli O128. It was found that methyl α- L -fucopyranoside was the most effective inhibitor amongst the monosaccharides while the highest antibody specificity was directed towards the trisaccharide with the structure: β- D -GalpNAc-(1→6)-[α- L -Fucp-(1→2)]-β- D -Galp-1→OMe suggesting that the monospecific antibody has the extended combining site.

The O-specific polysaccharide isolated from Escherichia coli O128 lipopolysaccharide contains d -galactose, l -fucose, and 2-acetamido-2-deoxy- d -galactose in the molar ratios 2:1:2. The primary structure of the O-specific polysaccharide from E. coli was established by compositional analysis, methylation analysis, together with 1 H and 13 C NMR spectroscopy including two-dimensional shift-correlated and one-dimensional NOE spectroscopy. The polysaccharide moiety was found to consist of a tetrasaccharide backbone containing d -galactose and 2-acetamido-2-deoxy- d -galactose, with l -fucose as a side chain in a branched pentasaccharide repeating unit having the following structure

Interconversions of Anilides from Malonic Ester

Cyclodehydration of 4-\(m\)-chloroa,nilino-8-methoxyquinoline-3-carboxylic acid (IX) and the corres­ponding 8-hydroxy compound (X) in cone. sulphuric acid yielded 4-inethoxy-7-hydroxy-10-chlorodibenzo [b,h][1,6] naphthyridine (XIV) and 4,7-dihydroxy-10-chlorodibenzo [b,h][1,6] naphthyridine (XV) res­pectively. The assigned structure was confirmed by an unequivocal cyclodehydration of 8-methoxy-4- (2-carboxy 5-chloro) anilinoquinoline (XVI) to (XIV). Treatment with phosphorus oxychioride converted XIV and XV to the corresponding 7-chloro derivatives respectively (XVII and XVIII).

Condensation of 4-hydroxy-7,10-dichlorodibenzo [\(b\), \(h\)] [1, 6] naphthyridine with 5-diethylamino­2-aminopentane and 4-amino -2 -diethylaminomethylphenol furnished 4-hydroxy -7- (4 - diethylami no -1 - methylbutylamino)-10-chlorodibenzo [\(b\), \(h\)] [1, 6] .naphthyridine and the corresponding 7-(4-hydroxy 3-diethylaminomethyl anilino) derivative respectively. Amino substituents underwent ready displace­ment in aqueous solution of their hydrochlorides and produced the 7-hydroxy derivative. Attempted Mannich reaction on 4,7-dihydroxy-10-chlorodibenzo [\(b\), \(h\)] [1, 6] naphthyridine resulted in the recovery of the unchanged material. Attempts to iodochlorinate the amino compounds at low temperature also failed.