Priprava ferocenskih amida manoziliranog desmuramil-dipeptida s potencijalnim adjuvantskim učinkom

master's thesis

• Title (english): Synthesys of ferrocene amides of mannosylated desmuramyl dipeptide with potential adjuvant activity
• Author: Ivona Bajan
• Mentor: Vesna Petrović Peroković (mentor)
• Committee member: Vesna Petrović Peroković (predsjednik povjerenstva)
• Committee member: Ivica Đilović (član povjerenstva)
• Committee member: Aleksandra Maršavelski (član povjerenstva)
• Committee member: Željka Car (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2022-09-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U sklopu ovog rada sintetizirana su tri ferocenska amidna derivata manoziliranog desmuramildipeptida s varirajućom duljinom ugljikovodičnog lanca između ferocena i ostatka molekule.
Ferocenski amini s tri i četiri metilenske skupine pripravljeni su iz odgovarajućih zaštićenih
amina uklanjanjem Boc zaštite dok je ferocenski amin s dvije metilenske skupine pripravljen
redukcijom iz ferocenacetonitrila. Kao peptidna podjedinica korišten je Boc-L-Ala-D-isoGln
koji je priređen uklanjanjem benzilne zaštitne skupine s odgovarajućeg komercijalno dostupnog
dipeptida Boc-L-Ala-D-isoGln(OBn). Manozna podjedinica pripravljena je iz 2,3,4,6-tetra-Oacetil-α-D-manopiranoze reakcijom s tert-butil-bromoacetatom te uklanjanjem tert-butilne
zaštitne skupine u kiselim uvjetima. Ferocenski amini najprije su amidnom vezom povezani s
desmuramil-dipeptidom preko karboksilne skupine bočnog ogranka isoGln reakcijom
kondenzacije uz EDC×HCl kao kondenzacijski reagens, HOBt kao aditiv te TEA kao bazu.
Nakon uklanjanja peptidne Boc zaštite, ferocenski amidni derivati desmuramil-dipeptida
povezani su s manoznom podjedinicom u istim uvjetima amidacije. Konačni korak u sintezi
ciljnih produkata bilo je uklanjanje acetilnih zaštitnih skupina s manozne podjedinice, što je
provedeno Zemplénovim postupkom te su uspješno pripravljeni produkti u svrhu ispitivanja
adjuvantskog učinka.

Abstract (english)

In this thesis, three ferrocene amide derivatives of mannosylated desmuramyl dipeptide with
varying length of the alkyl chain connecting the ferrocene subunit with the rest of the molecule
have been synthesized. Ferrocene amines with three and four methylene groups were prepared
from the corresponding protected amines by removal of the Boc protective group. Ferrocene
amine with two methylene groups has been prepared by reduction of ferroceneacetonitrile. BocL-Ala-D-isoGln was used as the peptide subunit and prepared by removing the benzyl protective
group from the corresponding commercially available Boc-L-Ala-D-isoGln(OBn). 2,3,4,6-
tetra-O-acetyl-α-D-mannopyranose was used for the preparation of the mannose subunit by its
reaction with tert-butyl bromoacetate and subsequent removal of the tert-butyl protective group
in acidic condition. Ferrocene amines were connected through an amide bond to desmuramyl
dipeptide via the carboxyl group located on the isoGln side chain. For this purpose reaction
with EDC×HCl as a condensation reagent, HOBt as an additive and TEA as a base was used.
After the removal of the peptide Boc protective group, ferrocene amide derivatives of
desmuramyl dipeptide were linked to the mannose subunit in the same amidation reaction
conditions. The final step in the synthesis of the target products was the removal of the acetyl
protective groups from the mannose subunit, which was achieved by Zemplén's procedure.
Thus, the final products were succesfully obtained and will be used for the investigation of their
adjuvant activity.

• Keywords: adjuvanti; amidacija; desmuramil-dipeptid; ferocen; manokonjugati
• Keywords (english): adjuvants; amidation; desmuramyl dipeptide; ferrocene; mannoconjugates
• Language: croatian
• URN:NBN: urn:nbn:hr:217:548880
• 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: 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: Embargoed access; Embargo expiration date: 2024-09-16
• Created on: 2022-10-06 12:04:30