Razvoj sintetskog puta za pripravu lipofilnih derivata desmuramil-dipeptida

master's thesis

• Title (english): Development of the synthetic route for the preparation of lipophilic desmuramyl dipeptide derivatives
• Author: Laura Nuić
• Mentor: Željka Car (mentor)
• Committee member: Biserka Prugovečki (predsjednik povjerenstva)
• Committee member: Željka Car (član povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Vesna Petrović Peroković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U sklopu diplomskog rada optimirana je metoda amidacije tert-butiloksikarbonil (Boc) zaštićenog dipeptida ʟ-alanil-ᴅ-izoglutamina lipofilnim aminskim prekursorima. Lipofilne su podjedinice (adamantil-triazolna, adamantilna, dodecilna) uvedene na bočni lanac ᴅ-izoglutamina (ᴅ-isoGln). Adamantilna podjedinica je uvedena na dipeptid preko komercijalno dostupnog 1-aminoadamantan hidroklorida i preko 1,2,3-triazolnog prstena, dobivenog bakrom(I) kataliziranom cikloadicijskom reakcijom iz Boc zaštićenog propargilamina. U toj reakciji je Boc zaštita uvedena in situ te naknadno uklonjena s trifluoroctenom kiselinom. Dodecilamin je pripravljen redukcijom odgovarajućeg azida s LiAlH4. Ispitane su tri metode amidacije. Osim iz kupovnog dipeptida adamantilna ciljna molekula izgrađena je potpuno drugačijim sintetskim pristupom uvođenjem 1-aminoadamantan hidroklorida na bočni ogranak Boc zaštićenog ᴅ-isoGln pomoću dvije najučinkovitije metode amidacije iz prethodnog pristupa. Zatim je uklonjena Boc zaštita te je lipofilni desmuramil-dipeptid dobiven konjugacijom s Boc zaštićenim N-hidroksisukcinimidnim esterom ʟ-alanina. Kao i u koracima prije, Boc zaštita uklonjena je standardnim postupkom.

Abstract (english)

In this Thesis the synthetic route for amidation of tert-butyloxycarbonyl (Boc) protected dipeptide ʟ-alanyl-ᴅ-isoglutamine with lipophilic amine precursors was optimized. Lipophilic subunits (adamantyl triazolyl, adamantyl, dodecyl) were introduced at the ᴅ-isoglutamine (ᴅ-isoGln) side chain. For the incorporation of adamantyl subunit commercially available 1-aminoadamantane hydrochloride was used. The same subunit was also incorporated through 1,2,3-triazole ring obtained via Copper Catalyzed Azide-Alkine Cycloaddition from Boc protected propargylamine. Boc protection was achieved in situ and then removed with trifluoroacetic acid. Dodecylamine was obtained by reduction of corresponding azide derivative with LiAlH4. Three amidation methods were investigated next. Adamantyl desmuramyl dipeptide was also prepared by completely different route starting from the Boc protected ᴅ-isoGln. Two most efficient, previously investigated, amidation methods were used for coupling of ᴅ-isoGln side chain with 1-aminoadamantane hydrochloride in the first step. Boc protection was removed and dipeptide prepared by condensation with Boc protected N-hydroxysuccinimide ester of ʟ-alanine. As in previous steps, Boc group was removed using standard procedure.

• Keywords: adamantan; adjuvanti; amidacija; desmuramil-dipeptid; dodecilamin; klik-reakcija
• Keywords (english): adamantane; adjuvants; amidation; click reaction; desmuramyl dipeptide; dodecylamine
• Language: croatian
• URN:NBN: urn:nbn:hr:217:728416
• 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: 2023-07-15
• Created on: 2021-08-27 11:44:24