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U sklopu ovog rada sintetizirana su tri ferocenska amidna derivata manoziliranog desmuramildipeptida s varirajućom duljinom ugljikovodičnog lanca između ferocena i ostatka molekule. Ferocenski amini s tri i četiri metilenske skupine pripravljeni su iz odgovarajućih zaštićenih amina uklanjanjem Boc zaštite dok je ferocenski amin s dvije metilenske skupine pripravljen redukcijom iz ferocenacetonitrila. Kao peptidna podjedinica korišten je Boc-L-Ala-D-isoGln koji je priređen uklanjanjem benzilne zaštitne skupine s odgovarajućeg komercijalno dostupnog dipeptida Boc-L-Ala-D-isoGln(OBn). Manozna podjedinica pripravljena je iz 2,3,4,6-tetra-Oacetil-α-D-manopiranoze reakcijom s tert-butil-bromoacetatom te uklanjanjem tert-butilne zaštitne skupine u kiselim uvjetima. Ferocenski amini najprije su amidnom vezom povezani s desmuramil-dipeptidom preko karboksilne skupine bočnog ogranka isoGln reakcijom kondenzacije uz EDC×HCl kao kondenzacijski reagens, HOBt kao aditiv te TEA kao bazu. Nakon uklanjanja peptidne Boc zaštite, ferocenski amidni derivati desmuramil-dipeptida povezani su s manoznom podjedinicom u istim uvjetima amidacije. Konačni korak u sintezi ciljnih produkata bilo je uklanjanje acetilnih zaštitnih skupina s manozne podjedinice, što je provedeno Zemplénovim postupkom te su uspješno pripravljeni produkti u svrhu ispitivanja adjuvantskog učinka. In this thesis, three ferrocene amide derivatives of mannosylated desmuramyl dipeptide with varying length of the alkyl chain connecting the ferrocene subunit with the rest of the molecule have been synthesized. Ferrocene amines with three and four methylene groups were prepared from the corresponding protected amines by removal of the Boc protective group. Ferrocene amine with two methylene groups has been prepared by reduction of ferroceneacetonitrile. BocL-Ala-D-isoGln was used as the peptide subunit and prepared by removing the benzyl protective group from the corresponding commercially available Boc-L-Ala-D-isoGln(OBn). 2,3,4,6- tetra-O-acetyl-α-D-mannopyranose was used for the preparation of the mannose subunit by its reaction with tert-butyl bromoacetate and subsequent removal of the tert-butyl protective group in acidic condition. Ferrocene amines were connected through an amide bond to desmuramyl dipeptide via the carboxyl group located on the isoGln side chain. For this purpose reaction with EDC×HCl as a condensation reagent, HOBt as an additive and TEA as a base was used. After the removal of the peptide Boc protective group, ferrocene amide derivatives of desmuramyl dipeptide were linked to the mannose subunit in the same amidation reaction conditions. The final step in the synthesis of the target products was the removal of the acetyl protective groups from the mannose subunit, which was achieved by Zemplén's procedure. Thus, the final products were succesfully obtained and will be used for the investigation of their adjuvant activity. |
