Priprava derivata manoziliranog desmuramil-peptida s ferocenskom podjedinicom na α-položaju D-izoglutamina

master's thesis

• Title (english): Synthesis of mannosylated desmuramyl peptide derivatives with a ferrocene subunit at α-position od D-isoglutamine
• Author: Filip Kučas
• Mentor: Vesna Petrović Peroković (mentor)
• Committee member: Vesna Petrović Peroković (predsjednik povjerenstva)
• Committee member: Dominik Cinčić (član povjerenstva)
• Committee member: Gordan Horvat (član povjerenstva)
• Committee member: Željka Car (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-12-15, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U sklopu ovog diplomskog rada sintetizirana su tri nova manozilirana derivata desmuramil-
peptida (DMP-a) s lipofilnom ferocenskom podjedinicom vezanom na α-kraj D-izoglutamina
pri čemu je varirana duljina ugljikovodične razmaknice između ferocena i peptidnog dijela
molekule. Aminoferocen je pripravljen uklanjanjem Boc-zaštitne skupine sa zaštićenog
aminoferocena, dok su aminometilferocen i (2-aminoetil)ferocen pripravljeni redukcijom
pripadnog amida, odnosno nitrila. Kao polazni peptid korišten je zaštićeni dipeptid L-alanil-D-
glutaminska kiselina (Boc-L-Ala-D-Glu(OBn)). Na α-kraj glutaminske kiseline DMP-a
amidnom vezom vezani su ferocenski amini s različitim brojem metilenskih skupina između
amino-skupine i ferocenske podjedinice reakcijom kondenzacije pomoću EDC/HOBt i HBTU
metode. Nakon uklanjanja Boc-zaštitne skupine s amino-skupine L-alanina u kiselim uvjetima,
amidni ferocenski derivati desmuramil-peptida vezani su amidnom vezom s benzilima
zaštićenom manoznom podjedinicom preko C2 razmaknice u istim uvjetima amidacije.
Posljednji korak u sintezi bio je uklanjanje benzilnih zaštitnih skupina sa šećernog dijela
molekule i benzilog estera s bočnog ogranka D-izoglutamina postupkom katalitičke
hidrogenolize čime su uspješno sintetizirane ciljne molekule kojima se ispituje adjuvantski
učinak.

Abstract (english)

In this diploma thesis, three new mannosylated derivatives of desmuramyl-peptide (DMP) were
synthesized with a lipophilic ferrocene subunit bonded to the α-end of D-isoglutamine, whereby
the length of the hydrocarbon spacer between ferrocene and the peptide part of the molecule
was varied. Aminoferrocene was prepared by removing the Boc-protecting group from
protected aminoferrocene, while aminomethylferrocene and (2-aminoethyl)ferrocene were
prepared by reduction of the corresponding amide and nitrile. The protected dipeptide L-alanyl-
D-glutamic acid (Boc-L-Ala-D-Glu(OBn)) was used as starting peptide. Ferrocene amines with
a different number of methylene groups between the amino group and the ferrocene subunit are
attached to the α-end of the glutamic acid of DMP via amide bond obtained by condensation
reaction using EDC/HOBt and HBTU methods. After removal of the Boc-protecting group
from the amino group of L-alanine under acidic conditions, amide ferrocene derivatives of
desmuramyl-peptide are bound by an amide bond with benzylated mannose subunit via the C2
spacer under the same amidation conditions. The last step in the synthesis was the removal of
the benzyl protecting groups from the sugar part of the molecule and the benzylic ester from
the D-isoglutamine side branch by the catalytic hydrogenolysis process in the end target
molecules were successfully obtained and where then tested for adjuvant activity.

• Keywords: adjuvansi; amidacija; desmuramil-peptid; ferocen; manoza
• Keywords (english): adjuvants; amidation; desmuramyl-peptide; ferrocene; mannose
• Language: croatian
• URN:NBN: urn:nbn:hr:217:456767
• Project: Number: IP-2020-02-9162; Title: Ferocenski analozi biomolekula: strukturna karakterizacija i biološka evaluacija; Title: Ferrocene analogues of biomolecules: structural characterization and biological evaluation; Acronym: FER-AN-BIOMOL; Leader: Lidija Barišić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Graduate university studies in chemistry; specializations in: Graduate university studies in chemistry; Course: Graduate university studies in chemistry; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra kemije (sveučilišni/a magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-12-15
• Created on: 2024-01-10 10:55:01