Totalna sinteza peniciklona A

doctoral thesis

• Title (english): Total synthesis of penicyclone A
• Author: Gregor Talajić
• Mentor: Nikola Cindro (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Davor Margetić (član povjerenstva)
• Committee member: Nikola Bregović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2024-06-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Peniciklon A je poliketid izoliran iz kulture dubokomorske gljivice Penicillium Sp. F32-2. Zanimljiva struktura ovog prirodnog spoja koji sadrži spiro[5.5]laktonsku jezgru i četiri stereogena centra te prijavljena antimikrobna aktivnost potaknule su studije o njegovoj totalnoj sintezi. U ovom radu istražena su tri fundamentalno različita pristupa sintezi peniciklona A. Prvi pristup temeljio se na razvoju oksidativne dearomatizacije fenola te daljnje funkcionalizacije dobivenog cikloheksadienona regioselektivnom cis-dihidroksilacijom. Drugi pristup temeljio se na korištenju D-(+)-kvininske kiseline kao polaznog spoja, dok se treći pristup temeljio na razvoju dijastereoselektivne dvostruke adicije Grignardovih reagensa na literaturno poznati lakton izveden iz D-riboze. Peniciklon A je uspješno pripravljen trećim pristupom. Sintetski peniciklon A pokazao je različito optičko skretanje od prirodnog materijala te nedostatak antimikrobne aktivnosti što je potaknulo sintezu i drugog enantiomera, također iz D-riboze.

Abstract (english)

Penicyclone A is a polyketide isolated from the deep-sea fungus Penicillium Sp. F32-2. Its interesting structure containing a spiro[5.5]lactone core and four stereogenic centers and the reported antimicrobial activity prompted studies in its total synthesis. Three fundamentally different approaches to the synthesis of penicyclone A were investigated. The first approach was based on the development of an oxidative dearomatization of phenols and further functionalization of the obtained cyclohexadienone by regioselective cis-dihydroxylation. The second approach was based on the use of D-(-)-quinic acid as a starting compound, while the third approach was based on the development of a diastereoselective double Grignard reaction. Penicyclone A was successfully prepared using the third approach. Synthetic penicyclone A showed differences in optical rotation and a lack of antimicrobial activity. This prompted the synthesis of the second enantiomer.

• Keywords: antibiotik; Grignardova reakcija; poliketid; totalna sinteza
• Keywords (english): antibiotic; Grignard reaction; polyketide; total synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:979873
• Promotion: 2024
• Study programme: Title: Doctoral study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica u području prirodnih znanosti (doktor/doktorica u području prirodnih znanosti)
• Type of resource: Text
• Extent: 118, CLXXVI str. ; 30 cm
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-06-14
• Created on: 2024-06-21 11:58:26