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.
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.
Ledvina
M
M
Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague.
Jezek
J
J
Saman
D
D
Vaisar
T
T
Hríbalová
V
V
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced; D007111:Immunity, Cellular; D008969:Molecular Sequence Data; D011749:Pyrogens; D011817:Rabbits
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D004187:Disaccharides; C086576:O-(2-acetamido-2-deoxy-6-O-(2-tetradecylhexadecanoyl)glucopyranosyl)-1-4-N-acetylnormuramoyl-alpha-aminobutanoyl-isoglutamine; C086575:O-(2-acetamido-2-deoxy-6-O-stearoylglucopyranosyl)-1-4-N-acetylnormuramoyl-alpha-aminobutanoyl-isoglutamine; D011749:Pyrogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine