Synthesis of O-[2-acetamido-2-deoxy-6-O-stearoyl- and -6-O-(2-tetradecylhexadecanoyl)-beta-D-glucopyranosyl]-(1-->4)-N- acetylnormuramoyl-L-alpha-aminobutanoyl-D-isoglutamine, lipophilic disaccharide analogues of MDP

Carbohydr Res. 1994 Jan 3:251:269-84. doi: 10.1016/0008-6215(94)84291-4.

Abstract

Silver triflate-promoted condensation of 3,4,6-tri-O-acetyl-2-deoxy-2- phthalimido-beta-D-glucopyranosyl bromide (1) with benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O- (methoxycarbonyl)methyl-alpha-D-glucopyranoside (4) afforded the key compound, benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O- (methoxy-carbonyl)methyl-4-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-b eta-D- glucopyranosyl)-alpha-D-glucopyranoside (5), which after deprotection was transformed into acid 10. Condensation of 10 with the benzyl ester of L-alpha-aminobutanoyl-D-isoglutamine and deisopropylidenation of the product 11 afforded the benzyl ester of N-(2-O-[benzyl 2-acetamido-4-O-(2-acetamido-3-O-benzyloxymethyl-2- deoxy-beta-D-glucopyranosyl)-6-O-benzyl-2,3-dideoxy-alpha-D-glucopyra nosid-3- yl]glycoloyl)-L-alpha-aminobutanoyl-D-isoglutamine (12). Partial O-acylation of 12 and hydrogenolysis of protecting groups gave the 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-disaccharide-dipeptides 17 and 18, respectively. Pyrogenicity and adjuvant activity in cell-mediated immunity are reported.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
  • Acetylmuramyl-Alanyl-Isoglutamine / chemical synthesis
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Adjuvants, Immunologic / chemistry*
  • Animals
  • Antineoplastic Agents / chemistry*
  • Carbohydrate Sequence
  • Disaccharides / chemical synthesis*
  • Disaccharides / chemistry*
  • Disaccharides / pharmacology
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Immunity, Cellular
  • Molecular Sequence Data
  • Pyrogens
  • Rabbits

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Disaccharides
  • O-(2-acetamido-2-deoxy-6-O-(2-tetradecylhexadecanoyl)glucopyranosyl)-1-4-N-acetylnormuramoyl-alpha-aminobutanoyl-isoglutamine
  • O-(2-acetamido-2-deoxy-6-O-stearoylglucopyranosyl)-1-4-N-acetylnormuramoyl-alpha-aminobutanoyl-isoglutamine
  • Pyrogens
  • Acetylmuramyl-Alanyl-Isoglutamine