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Optimization of synthetic route to ferrocene esters of desmuramyl dipeptides

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 synthesis. In order to prepare such compounds lipophilic DMP precursors are needed (Fig. 1a). Lipophilic subunits used so far have been adamantyl, adamantyl triazolyl, dodecyl and were introduced through an amide bond at the side chain or on α-carbon atom of D-isoGln residue. In this work we are optimizing the synthesis of ferrocene esters of DMP. The lipophilic ferrocene part is introduced on the D-isoGln side chain via several ferrocene alcohols (Fig. 1b). [2] In order to obtain the ester bond modified Steglich procedure was envisioned. In the case of ferrocenemethanol this procedure was not successful due to low nucleophilicity of its hydroxyl group. Therefore, in this work, several other methods for the preparation of its ester were explored.

adjuvants ; muramyl dipeptide ; desmuramyl peptide ; ferrocene esters of DMP ; ferrocene alcohols

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