Dialkylmethyl beta-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: synthesis and infection protective and cytotoxic activities
Zemliakov, A.E.; Tsikalova, V.N.; Tsikalov, V.V.; Chirva, V.I.; Mulik, E.L.; Kuzovlev, F.N.; Kaliuzhin, O.V.; Kiselevskií, M.V.
Bioorganicheskaia Khimiia 34(1): 114-120
2008
ISSN/ISBN: 0132-3423 PMID: 18365746 Document Number: 615390
Symmetric secondary linear alcohols were proposed as aglycones for the synthesis of lipophilic beta-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). Pentadecan-8-ol, nonadecan-10-ol, and tricosan-12-ol were glycosylated by the oxazoline method. Based on the corresponding glucosaminides, alkyl beta-glycosides of 4,6-O-isopropylidene-N-acetylmuramic acid were synthesized and coupled with the dipeptide. Deprotection of isopropylidene groups by acidic hydrolysis and catalytic hydrogenolysis of benzyl esters resulted in the target muramyldipeptide glycosides. Nonadecan-10-yl and tricosan-12-yl β-MDPs at doses 2 microg/mice most effectively stimulated antibacterial resistance in mice against Staphylococcus aureus. In contrast to the previously synthesized undecan-6-yl beta-MDP, pentadecan-8-yl, nonadecan-10-yl, and tricosan-12-yl beta-MDPs demonstrated direct cytotoxicity toward tumor cells E-562 and blood mononuclear cells.