| Popis: |
U sklopu diplomskog rada opisana je priprava triju novih alifatskih triazolnih derivata manoziliranog desmuramil-dipeptida, L-Ala-D-isoGln. U konvergentnom pristupu sintezi zasebno su pripravljene tri podjedinice: dipeptid, alifatski triazolni amin i manozna podjedinica, koje su zatim međusobno povezane amidnim vezama. Kao polazni dipeptid iz odgovarajućih zaštićenih aminokiselina pripravljen je Boc-L-Ala-D-Glu(OBn). Alifatske triazolne podjedinice pripravljene su klik-reakcijom, bakrom(I) kataliziranom azid-alkinskom cikloadicijom (CuAAC) Boc-zaštićenog propargilamina i odgovarajućih azida, heksadecil-azida i 2- (adamant-1-il)etil-azida. Nakon uklanjanja Boc zaštite dobiveni alifatski triazolni amini te prethodno pripravljen dodecilni analog vezani su amidnom vezom na α-karboksilnu skupinu dipeptida Boc-L-Ala-D-Glu(OBn). Benzilima zaštićena manozna podjedinica s acetilnom poveznicom pripravljena je hidrolizom odgovarajućeg estera. Alifatski triazolni derivati desmuramil-dipeptida nakon uklanjanja Boc zaštite vezani su preko amino-skupine alanina na karboksilnu skupinu manozne podjedinice. U zadnjem koraku reakcije uklanjanjem svih benzilnih zaštitnih skupina reakcijom katalitičke hidrogenolize uspješno su pripravljene ciljne molekule ovog rada kojima je konačni cilj ispitati in vivo adjuvantsku aktivnost. In this diploma thesis, the preparation of three new lipophilic aliphatic triazole derivatives of manosylated desmuramyl dipeptide, L-Ala-D-isoGln, were described. In the convergent synthesis approach, three subunits were prepared separately: the dipeptide, the aliphatic triazole amine, and the mannose subunit, which were then interconnected by amide bonds. Boc-L-AlaD-Glu(OBn) was prepared as the starting dipeptide from the corresponding protected amino acids. Aliphatic triazole subunits were prepared by click reaction, copper(I) catalyzed azidealkyne cycloaddition (CuAAC) of Boc-protected propargylamine and the corresponding azides, hexadecyl-azide and 2-(adamant-1-yl)ethyl-azide. After the removal of Boc, the resulting aliphatic triazole amines and the previously prepared dodecyl analog were attached by an amide bond to the α-carboxyl group of the dipeptide Boc-L-Ala-D-Glu(OBn). The benzyl-protected mannose subunit with an acetyl linker was prepared by hydrolysis of the corresponding ester. After removal of Boc-protection group aliphatic triazole derivatives of desmuramyl dipeptide were coupled through the carboxyl group of the mannose subunit and the amino groups of alanine. In the last reaction step, all benzyl protecting groups were removed by the catalytic hydrogenolysis reaction and the target molecules of this work were successfully prepared with the final goal of testing their in vivo adjuvant activity. |
