Novi postupci priprave adamantil-triazolnih derivata manoziliranog desmuramil-dipeptida

master's thesis

• Title (english): A novel synthetic route to adamantyltriazole derivative of mannosylated desmuramyl dipeptide
• Author: Josip Draženović
• Mentor: Vesna Petrović Peroković (mentor)
• Committee member: Vesna Petrović Peroković (predsjednik povjerenstva)
• Committee member: Davor Kovačević (član povjerenstva)
• Committee member: Predrag Novak (član povjerenstva)
• Committee member: Ivana Biljan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2020-06-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U sklopu diplomskog rada ispitana je mogućnosti priprave adamantil-triazolnog derivata desmuramildipeptida,
L-Ala-D-isoGln, koji je dodatno modificiran uvoĎenjem manozne podjedinice vezane za
dipeptid preko acetilne poveznice. Kao peptidni prekursor pripravljen je zaštićeni dipeptid Boc-L-Ala-
D-Glu(OBn), a na istome je uspješno provedena reakcija amidacije s propargilaminom uz Nmetilmorfolin
te n-butil-klorformijat kao kondenzacijski reagens. Metoda amidacije optimirana je i
uspješno iskorištena i prilikom uvoĎenja adamantil-triazolne podjedinice u strukturu dipeptida.
Adamantil-triazolna podjedinica pripravljena je „one-pot“ sintezom iz komercijalno dostupnog
propargilamina i prethodno pripravljenog 1-azidoadamantana. Optimirana „one-pot“ sinteza uspješno
je upotrijebljena u laboratoriju za pripravu novih 1,4-supstituiranih triazolnih derivata propargilamina.
U klik-reakciji koja je dio „one-pot“ sinteze kao katalizator korišten je in situ generirani bakar(I).
Prethodno pripravljena benzilima zaštićena manoza preko acetilne poveznice u reakciji kondenzacije
povezana je s propargiliranim dipeptidom i adamantil-triazolnim derivatom desmuramil-dipeptida.
Konačni cilj diplomskog rada je pripravljanje izomerno čistog manoziliranog adamantil-triazolnog
derivata desmuramil-dipeptida kojem je po pripravi potrebno in vivo ispitati adjuvantsku aktivnost.

Abstract (english)

In this diploma thesis, the possibilities of preparation of the adamantyltriazole derivative of
desmuramyldipeptide, which was further modified by the introduction of a mannose subunit bound to
the dipeptide via an acetyl linker, were investigated. The protected dipeptide Boc-L-Ala-D-Glu-(OBn)
was prepared first as a peptide precursor and then modified successfully in the amidation reaction with
propargylamine. In this reaction n-butyl chloroformate was used as the condensing reagent and Nmethylmorpholine
as a base. The amidation method was optimized and successfully applied for the
introduction of the adamantyltriazole subunit into the structure of the dipeptide. The adamantyltriazole
subunit was prepared by one-pot synthesis from commercially available propargylamine and
previously prepared azidoadamantane. Optimized one-pot synthesis has been successfully used in the
laboratory for the preparation of new 1,4-substituted triazole propargylamine derivatives. As a part of
the one-pot synthesis in situ-generated copper(I) was used as a catalyst. Previously prepared benzylprotected
mannose in the penultimate step of the overall synthesis is connected to a propargylated
dipeptide and an adamantyltriazole derivative of desmuramyldipeptide. The final goal of the diploma
thesis is the preparation of an isomerically pure deprotected manosylated adamantyltriazole derivative
of desmuramyldipeptide. Adjuvant activity will be tested in vivo on the prepared target molecule.

• Keywords: adamantan; adjuvanti; desmuramil-dipeptid; klik-kemija; manokonjugat; triazol
• Keywords (english): adamantane; adjuvant; desmuramyldipeptide; click-chemistry; mannoconjugates; triazole
• Language: croatian
• URN:NBN: urn:nbn:hr:217:218690
• 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: 2022-06-19
• Created on: 2020-07-20 09:38:16