Synthesis and biological activity of O-( N-acetyl-β-muramoyl- l-alanyl- d-isoglutamine)-(1→6)-2-acylamino-2-deoxy- d-glucoses

Abstract

Benzoylation of benzyl 2-acetamido-2-deoxy-4,6- O-isopropylidene-α- d-glucopyranoside, benzyl 2-deoxy-2-( dl-3-hydroxytetradecanoylamino)-4,6- O-isopropylidene-α- d-glucopyranoside, and benzyl 2-deoxy-4,6- O-isopropylidene-2-octadecanoylamino-β- 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]-α- 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-(methoxycarbonyl)ethyl]-β- 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→6)-β-linked disaccharide derivatives 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-β-muramoyl- l-alanyl- d-isoglutamine)-(1→6)-2-acylamino-2-deoxy- d-glucoses in good yields. The immunoadjuvant activity of these compounds was examined in guinea-pigs.