engleski

Synthesis of ferrocene ester derivatives of desmuramyl peptide

Derivatives of muramyl dipeptide (MDP), a well- known peptidoglycan fragment, have been extensively studied as possible adjuvants for human and animal vaccines. [1] MDP analogues without the N- acetylmuramyl moiety are called desmuramyl peptides (DMP). Structure-activity studies of the MDP derivatives and their analogues suggest that L-Ala- D-isoGln pharmacophore is essential for the immunostimulatory properties and that the introduction of lipophilic substituent can increase its adjuvant activity. In our previous research we reported the synthesis and immunostimulatory activity of DMP with an adamantane group on L-Ala-D-iGln fragment. [2] Furthermore, we prepared and biologically evaluated mannosylated adamantane derivatives of DMP which showed enhanced immunostimulatory activity compared to compounds without the mannose subunit. The acitivity of such compounds was additionally positively influenced by the glycolyl spacer between mannose unit and desmuramyl peptide. [3] The two bioorganometallic analogues of MDP bearing lipophilic ferrocene subunit were also previously synthesized by our group. [4] In this work we described the synthesis of novel class of DMP derivatives in which lipophilic ferrocene unit was introduced at C-terminus of L- Ala-D-iGln via ester bond, followed by mannosylation of N-terminus through glycolyl spacer. Furthermore, alkyl spacers of different length will also be introduced between desmuramyl peptide and ferrocene unit to further increase lipophilicity of the synthesized compounds. This work has been fully supported by Croatian Science Foundation under the project IP-2020-02- 9162. 1. R. Ribić, M. Paurević, S. Tomić, Croat. Chem. Acta 92 (2019) 153-161. 2. (a) R. Ribić, L. Habjanec, B. Vranešić, R. Frkanec, S. Tomić, Chem. Biodivers. 9 (2012) 777- 788., (b) R. Ribić, L. Habjanec, R. Frkanec, B. Vranešić, S. Tomić, Chem. Biodivers. 9 (2012) 1373- 1381. 3. R. Ribić, R. Stojković, L. Milković, M. Antica, M. Cigler, S. Tomić, Beilstein J. Org. Chem. 15 (2019) 1805- 1814. 4. L. Barišić, M. Roščić, M. Kovačević, M. Čakić Semenčić, Š. Horvat, V. Rapić, Carbohydr. Res. 346 (2011) 678-684.

adjuvant activity, desmuramyl peptide, ester bond, ferrocene alcohols

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