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Preparation of diamide derivatives of a disubstituted ferrocene with desmuramyl peptide and mannose subunit

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D- isoglutamine, MDP) is the smallest structural unit of peptidoglycans showing immunostimulating activity. [1] MDP analogues without the hydrophilic N-acetylmuramyl moiety are called desmuramyl peptides (DMP) and are extensively studied by our group as potential new adjuvants. [1] This work is a continuation of our ongoing SAR study of amphiphilic mannosyl DMP analogues and their adjuvant activity in which lipophilic subunits used so far have been adamantyl, adamantyl triazolyl, dodecyl. [2] Herein, we are optimizing the synthesis of diamide derivatives of disubstituted ferrocenes with DMP and mannose subunit (Fig. 1a). The key structures in this syntheses will be disubstituted ferrocene ester amines with various alkyl chain lenghts (n = 0-4, Fig. 1b) which will be also prepared starting from ferrocenecarboxylic acid. Disubstituted precursors will be connected to O-benzyl protected mannose through glycol linker at the amine part and, after removal of methyl ester by saponification, to benzyl protected DMP. Commercially available Boc- L-Ala-D-isoGln-OBn will be used for this purpose and subsequently deprotected at the L-alanyl part in standard acidic conditions (TFA). The final step in the syntheses of these compounds will be removal of all benzyl protecting groups by hydrogenolysis.

adjuvant ; desmuramyl peptide ; lipophilic unit ; mannose

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