Adicija triazolnih reagenasa na trostruku vezu derivata propinske kiseline: sinteza i karakterizacija

master's thesis

• Title (english): Addition of triazole reagents to triple bonds of propiolic acid derivatives: Synthesis and characterisation
• Author: Tomislav Gojšić
• Mentor: Srećko Kirin (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Vladimir Stilinović (član povjerenstva)
• Committee member: Ivica Đilović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-06-01, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

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.

Abstract (english)

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.

• Keywords: hidroaminacija; HOBt; propiolat; klik -kemija; sinteza peptidne veze
• Keywords (english): click chemistry; coupling reagents; hidroamination; HOBt; propiolate
• Language: croatian
• URN:NBN: urn:nbn:hr:217:783304
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-06-01
• Created on: 2021-07-13 11:25:19