Synthesis and Biological Activity of the Lipophilic Derivatives ofN- Acetyl-1-thiomuramoyl-l-alanyl-d-isoglutamine

Abstract

A variety of the lipophilic derivatives at C-l and C-6 in N-[2-0-(2-acetamido-2,3-dideoxy-lthio-{3-D-glucopyranose-3-yl)-D-Iactoyl]-L-alanyl-(N1-fatty acyl)-D-isoglutamine methyl esters were synthesized from 2-N-acetyl-l-S-acetyl-4,6-0-isopropylidene-l-thiomuramoyl-L-alanyl-D-isoglutamine methyl ester. Their immunoadjuvant activity in guinea-pigs, and the protective effect in mice infected with Escherichia coli (E-77156) were examined. 2095Recently, it has been shown that the introduction 1 '" 7) of fatty acyl groups as a lipophilic character at the restrict~d position of the sugar skeleton or dipeptide moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) and in its carbohydrate analogs that carry strong immunoadjuvant activity causes potent antitumor or anti-infection activity, based on the immune reaction, that is not found with MDP itself, and abolishes the pyrogenicity ·or necrotic inflammation that is a side effect with MDP.