Synthesis and biological activity of O-N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 leads to 6)-2-acylamino-2-deoxy-D-glucoses.
Benzoylation of benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-alpha-D-glucopyranoside, benzyl 2-deoxy-2-(DL-3-hydroxytetradecanoylamino)-4,6-O-isopropylidene-alpha-D-glucopyranoside, and benzyl 2-deoxy-4,6-O-isopropylidene-2-octadecanoylamino-beta-D-glucopyranoside, with subsequent hydrolysis of the 4,6-O-isopropylidene group, gave the corresponding 3-O-benzoyl derivatives (4, 5, and 7). Hydrogenation of benzyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[D-1-(methoxycarbonyl)ethyl]-alpha-D-glucopyranoside, followed by chlorination, gave a product that was treated with mercuric actate to yield 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[D-1-(methoxy-carbonyl)ethyl]-beta-D -glucopyranose (11). Treatment of 11 with ferric chloride afforded the oxazoline derivative, which was condensed with 4, 5, and 7 to give the (1 goes to 6)-beta-linked disaccharide derivative 13, 15, and 17. Hydrolysis of the methyl ester group in the compounds derived from 13, 15, and 17 by 4-O-acetylation gave the corresponding free acids, which were coupled with L-alanyl-D-isoglutamine benzyl ester, to yield the dipeptide derivatives 19-21 in excellent yields. Hydrolysis of 19-21, followed by hydrogenation, gave the respective O-(N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 goes to 6)-2-acylamino-2-deoxy-D-glucoses in good yields. The immuno-adjuvant activity of these compounds was examined in guinea-pigs.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000096:biosynthesis*; D000276:Adjuvants, Immunologic; D000818:Animals; D002236:Carbohydrate Conformation; D006020:Glycopeptides / Q000096:biosynthesis*; D006168:Guinea Pigs; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D013053:Spectrophotometry
D000276:Adjuvants, Immunologic; D006020:Glycopeptides; D007202:Indicators and Reagents; D000119:Acetylmuramyl-Alanyl-Isoglutamine