Izolacija i derivatizacija saponina iz ekstrakta kore drveta Quillaja saponaria u svrhu priprave konjugata s desmuramil-dipeptidom

master's thesis

• Title (english): Isolation and derivatization of saponin from the extract of Quillaja saponaria tree bark for the synthesis of conjugates with desmuramyl dipeptide
• Author: Ivan Logožar
• Mentor: Đani Škalamera (mentor)
• Committee member: Đani Škalamera (predsjednik povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Jana Pisk (član povjerenstva)
• Committee member: Vesna Petrović Peroković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-11-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Za sintezu konjugata Quillaja saponina i desmuramil-dipeptida u ovom diplomskom radu pripravljena
su tri ključna prekursora. Konjugacija triterpenskog saponina i desmuramil dipeptida planirana je
preko D-galakturonske kiseline, koja je izosterička s D-fukozom, prisutnom u prirodnom QS-21.
Derivat D-galakturonse kiseline potreban za sintezu konjugata bit će pripravljen u nekoliko koraka
polazeći iz komercijalno dostupne D-galakturonske kiseline monohidrata. Triterpenski saponin biti će
izoliran iz komercijalno dostupnog ekstrakta kore QS, nakon čega će biti zaštićen odgovarajućim
zaštitnim skupinama. Desmuramil dipeptid sintetizirat će se polazeći iz odgovarajućih amonikiselina.
Rad će uključivati izolaciju, derivatizaciju i karakterizaciju prirodnih spojeva sintetske metode
peptidne ugljikohidratne kemije. Cilj rada je pronalazak efikasnog sintetskog puta do ključnih
prekursora potrebnih za pripravu konjugata Quillaja saponina i desmuramil-dipeptida. Ove dvije
jedinice zasebno posjeduju izraženu imunoadjuvantsku aktivnost pa je pretpostavka da će njihovo
povezivanje dovesti do sinergističkog efekta u povećanju aktivnosti. Također, uloga šećernog dijela
nije zanemariva, jer je poznato da oblik u kojem se nalazi šećer kod derivata Quillaja saponina
(slobodne OH skupine ili u obliku acetilnih estera) može značajno promijeniti smjer imunološkog
odgovora (Th1/Th2).

Abstract (english)

Three key intermediates needed for the synthesis of Quillaja saponin and desmuramyldipeptide
conjugate were prepared in this diploma thesis. Conjugation of the triterpene precursor and
desmuramyldipeptide was planned through D-galacturonic acid, which is isosteric with D-fucose,
which occurs naturally in QS-21. D-Galacturonic acid derivative needed for this synthesis will be
prepared in a few steps, starting from commercially available D-galacturonic acid monohydrate. The
triterpene precursor will be isolated from commercially available Quillaja saponaria tree bark extract,
after which it will be protected by appropriate protective groups. Desmuramyldipeptide will be
prepared from its corresponding aminoacids. This thesis will include isolation, derivatization and
characterization of natural compounds, as well as, synthetic methods of peptide and carbohydrate
chemistry. The goal of this thesis was to find the most efficient synthetic pathway to these precursors
needed to prepare Quillaja saponin and desmuramyldipeptide conjugate. These two precursors have
extraordinary immunoadjuvant activity by themselves, and the ultimate goal is to show the synergistic
effect by combining the two. The sugar component is also crucial in this conjugate, as it can
drastically change the direction of the immune response (Th1/Th2).

• Keywords: cjepiva; derivati prirodnih spojeva; desmuramil-dipeptid; imunoadjuvanti; Quillaja saponini
• Keywords (english): desmuramyldipeptide; immunoadjuvant activity; natural compound derivates; Quillaja saponins; vaccines
• Language: croatian
• URN:NBN: urn:nbn:hr:217:578503
• 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: 2023-11-17
• Created on: 2021-12-06 12:58:48