Addition of triazole reagents to triple bonds of propiolic acid derivatives: Synthesis and characterisation

U ovom radu su istraţene adicije triazolnih reagensa 1-hidroksibenzotriazol (HOBt), N,N,N′,N′- tetrametil-O-(1H-benzotriazol-1-il)uronijev heksafluorofosfat (TBTU) i N-[(dimetilamino)-1H-1,2,3- triazolo-[4,5-b]piridin-1-ilmetilen]-N-metilmetanaminijev heksafluorofosfat N-oksid (HATU) na trostruku vezu propinske kiseline i njenog metilnog estera, te sinteza peptidne veze propinske kiseline uz navedene triazolne reagense i uz netriazolni reagens (1-cijano-2-etoksi-2- oksoetilidenaminooksi)dimetilaminomorfolinokarbonijev heksafluorofosfat (COMU). Adicija je proučena na reakciji s metil-propiolatom, dobiven je produkt O- adicije i na propinskoj kiselini u tandemu s sintezom peptidne veze s (1S,2S)-trans-N-Boc-1,2-diaminocikloheksanom, te je dobiven i produkt N- adicije. U reakciji HOBt i metil-propiolata je sintetiziran i pseudo-dimer, nastao od jedne molekule HOBt i dvije molekule metil-propiolata. UtvrĎeno je da je HOBt primarno odgovoran za adiciju. O- adicije su uočene u reakcijama s metil-propiolatom, dok je N- adicija uočena u reakciji s propinskom kiselinom. NMR spektri upućuju na nastanak jednog produkta N- adicije u reakcijama s metil-propiolatom. Korištenjem reagensa COMU-a sintetiziran je ciljni peptid s terminalnom trostrukom vezom.The subject of this thesis is the addition of triazolic reagents 1-hydroxybenzotriazole (HOBt), N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (TBTU) and N- [(dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) to the triple bond of propiolic acid and its methyl ester, and peptide coupling of propiolic acid with either mentioned triazolic reagents or non-triazolic reagent (1- cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU). The addition has been observed in the reaction with methyl-propiolate, where O- addition products have been isolated, and in the reaction with propiolic acid in tandem with peptide coupling with (1S,2S)-trans-N-Boc-1,2-diaminocyclohexane, where N- addition product has been isolated. In the reaction of HOBt and methyl-propiolate a pseudo dimer has been isolated, consisting of one molecule of HOBt and two molecules of methyl-propiolate. HOBt has been observed to be susceptible for the addition. O- additions were observed in reactions with methyl-propiolate, while N- addition was observed in reaction with propiolic acid. NMR spectra indicated that one product in the reactions with methyl-propiolate is a product of N- addition. By using reagent COMU the target peptide has been synthesized