Synthesis of a diamide derivative of a disubstituted ferrocene with desmuramyl-peptide and mannose subunit

U sklopu ovog diplomskog rada razvijen je sintetski put priprave amidnih, disupstituiranih ferocenskih derivata s desmuramil-peptidnom (DMP) i manoznom podjedinicom. Derivati se međusobno razlikuju u broju metilenskih skupina (n = 0-4) na poveznici između ferocenskog i šećernog dijela molekule. U ovom je radu pripravljena ciljna molekula 11, s poveznicom od četiri metilenske skupine i to vezanjem sljedećih strukturnih motiva: O-benzil zaštićene manoze s glikolnom poveznicom, ferocenkarboksilne kiseline koja je esterificirana, a potom i modificirana anhidridom glutarne kiseline u disusptituiranu ferocensku kiselinu 6, te benzilom zaštićenog derivata DMP-a 7. Amidne veze su ostvarene pomoću pouzdane i uhodane EDC/HOBt metode koja se često koristi u tu svrhu u peptidnoj kemiji. Sintetski put priprave ciljne molekule završava korakom uklanjanja benzilne zaštite hidrogenolizom. Provedena je detaljna strukturna karakterizacija svih sintetiziranih prekursora i konačnog spoja (1H, DEPTQ NMR i IR spektroskopija, spektrometrija masa ESI-MS). Ovako optimizirana metoda poslužit će za sintezu preostalih spojeva ove serije u budućim istraživanjima čiji je konačni cilj ispitivanje njihove adjuvantske aktivnosti.In this Thesis the synthetic route for the preparation of amide, disubstituted ferrocene derivatives with desmuramyl peptide (DMP) and mannose subunit was optimized. The structures of final compounds vary in the number of methylene groups (n = 0-4) between the ferrocene and the sugar part of the molecule. Target molecule 11, which has four methylene groups, was prepared in this work by combining following structural motifs: O-benzyl protected mannose with glycolic linker, ferrocene carboxylic acid which was converted to ester first and subsequently modified with glutaric anhydride to disubstituted ferrocene acid 6, and benzyl protected DMP derivative 7. Amide bonds are formed by reliable and wellestablished EDC/HOBt method which is often used in peptide synthesis for this purpose. The synthetic route to target molecule ends with benzyl protection removal by hydrogenolysis. Structural characterization of all precursors as well as target compound was performed by 1H, DEPTQ NMR and IR spectroscopies as well as mass spectrometry (ESI-MS). Optimized synthetic route presented here will serve for the preparation of remaining compounds in this series. The final aim is the evaluation of their adjuvant activity