Synthesis and biological activity of O-N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 leads to 6)-2-acylamino-2-deoxy-D-glucoses

Carbohydr Res. 1982 Mar 1:100:235-45. doi: 10.1016/s0008-6215(00)81038-1.

Abstract

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.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives
  • Acetylmuramyl-Alanyl-Isoglutamine / biosynthesis*
  • Adjuvants, Immunologic*
  • Animals
  • Carbohydrate Conformation
  • Glycopeptides / biosynthesis*
  • Guinea Pigs
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Optical Rotation
  • Spectrophotometry

Substances

  • Adjuvants, Immunologic
  • Glycopeptides
  • Indicators and Reagents
  • Acetylmuramyl-Alanyl-Isoglutamine