Design and synthesis of new glucosamine derivatives for the application in transition-metal catalytic systems

Kobaltovi katalizatorji se v zadnjih letih vedno bolj uporabljajo za tvorbo vezi ogljik-ogljik. Prednost kobalta pred ostalimi prehodnimi kovinami je predvsem njegova dostopnost, nizka toksičnost ter nizka cena. Zaradi naštetih razlogov spadajo katalitski sistemi, ki kot katalizator uporabljajo kobaltove komplekse, med bolj ekološke. Reakcije z njimi potekajo v dokaj milih pogojih, za potek reakcije pa potrebujemo še bazo in ligand, s katerim kobalt tvori kompleks predhodno, ali pa in-situ. Tekom izdelave magistrske naloge smo sintetizirali nove derivate glukozamina kot ligande za katalitske sisteme. V teh sistemih z uporabo Grignardovih reagentov in s pomočjo kobalta in ligandov stereoselektivno tvorimo nove vezi ogljik-ogljik. Sintetizirali smo 8 potencialnih ligandov, od katerih smo nato tri uporabili v izbranem katalitskem sistemu. Sintetizirane spojine smo testirali tudi na encimih acetilholinesteraza, butirilholinesteraza in monoaminooksidaza A in B. Zaviralno aktivnost sta izkazovali dve spojini, in sicer na encimu butirilholinesteraza. Nazadnje smo ligandom določili tudi sposobnost kelacije nekaterih prehodnih kovin. Komplekse s kobaltom (Co2+) je tvorilo šest spojin, z železom (Fe2+) pa ena. Spojine, sposobne kelacije prehodnih kovin, se lahko potencialno uporabijo kot zdravilne učinkovine, kot kelatorji, ali pa kot učinkovine, kjer je prehodna kovina del zdravilne učinkovine in igra pri klinični aplikaciji ključno vlogo. Anorganska farmacevtska kemija je v uporabi sicer še vedno na drugem mestu za organsko kemijo, a številne raziskave v zadnjem desetletju dokazujejo njen potencial na številnih področjih medicine in farmacije. Sintetizirane derivate glukozamina smo tako uporabili za tri različne namene: - kot ligande v katalitskih sistemih, kjer smo tvorili nove vezi ogljik-ogljik- kot potencialne zaviralce encimov AChE, BChE, MAO-A in MAO-B- kot kelatorje nekaterih prehodnih kovin.Cobalt-based catalytic systems are being more widely used in the carbon-carbon bond formation. In comparison to some other transition metals, cobalt is easily accessible, has low toxicity and lower cost, which makes cobalt-based catalytic systems more eco-compatible and eco-friendly. Reactions take place under mild conditions. For the reaction to occur, a base and a ligand need to be added. The ligand forms a complex with the cobalt, either beforehand or in-situ. This Master\u27s thesis is focused on the design of new glucosamine derivatives, to be used as ligands in catalytic systems, where carbon-carbon bonds were formed stereoselectively, using Grignard reagents and cobalt as a catalyst. We synthesised 8 potential ligands, of which three were used as ligands in the catalytic system. We tested the synthesised compounds on enzymes: acetylcholinesterase, butyrylcholinesterase, monoamino oxidase A and monoamino oxidase B. Two compounds showed inhibitory activity on butyrylcholinesterase. Lastly, we determined the ligands\u27 chelating ability of certain transition metals. Six compounds formed complexes with cobalt (Co2+), whereas one compound formed complexes with iron (Fe2+). Compounds with chelating abilities can potentially be used as drugs – either as drugs that target metal ions in some form (chelators), or metal-based drugs, where the metal ion is crucial to the clinical application. Pharmaceutical industry is still dominated by drugs of organic origin, but numerous researches in the past decade have shown the potential of the medicinal inorganic chemistry. Synthesised glucosamine derivates can potentially be used as: - ligands in catalytic systems, where carbon-carbon bonds are formed- inhibitors for AChE, BChE, MAO-A and MAO-B- chelators of certain transitiona metals