Dialkylmethyl beta -glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: Synthesis and protective antiinfection and cytotoxic activities

Symmetric secondary linear alcohols were proposed as aglycones for the synthesis of lipophilic glycosides of beta -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 beta -MDPs at doses 2 mu g/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 K-562 and blood mononuclear cells.