Sinteza možnih metabolnih produktov analoga FDDNP

Brodnik, Ana (author), Košmrlj, Janez (mentor)

2-(1-(4-((4-(Etil(2-(fluoro)etil)amino)fenil)etinil)fenil)etiliden)malononitril je zaradi ugodnih optičnih in vezavnih lastnosti ter možnosti radiofluoriranja obetavna molekulska sonda za diagnosticiranje tauopatij. Predviden je bil njen metabolizem in zasnovana sintezna pot za sintezo matične molekulske sonde in treh njenih predvidenih metabolnih produktov. V laboratoriju sta bila izvedena dva koraka sinteze 2-(1-(4-((4-((2-(fluoro)etil)amino)fenil)etinil)fenil)etiliden)malononitrila: jodiranje komercialno dostopnega anilinskega derivata in spajanje po Sonogashiri z mebinolom. Preostala sintezna pot je bila začrtana teoretično. Vključuje tvorbo terminanega acetilena, ki se ga lahko s ponovno reakcijo po Sonogashiri spoji z bromoacetofenonom. Po fluoriranju z DAST in Knoevenagelovi kondenzaciji z malononitrilom lahko sintetiziramo končna produkta 2-(1-(4-((4-((2-(fluoro)etil)amino)fenil)etinil)fenil)etiliden)malononitril in 2-(1-(4-((4-(etil(2-(fluoro)etil)amino)fenil)etinil)fenil)etiliden)malononitril.

• Language: Slovenian
• Keywords: molekulska sonda, metaboliti, sinteza, spajanje po Sonogashiri
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2020
• PID: 20.500.12556/RUL-119652
• COBISS.SI-ID: 30485507
• Publication date in RUL: 10.09.2020

Secondary language

• Language: English
• Title: Synthesis of possible metabolic products of an FDDNP analogue

Abstract

2-(1-(4-((4-(Ethyl(2-(fluoro)ethyl)amino)phenyl)ethynyl)phenyl)ethylidene)-malononitrile was found to be a promising molecular probe in diagnosticizing tauopathies due to its favorable optical and binding properties, as well as radiofluorinating possibility. Its metabolism was predicted and a synthetic pathway of the parent molecular probe and its three predicted metabolites was proposed. Started by iodination of a commercially available aniline derivative and followed by Sonogashira coupling to mebynol, the first two steps of the syntheis of 2-(1-(4-((4-((2-(fluoro)ethyl)amino)phenyl)ethynyl)phenyl)ethylidene)-malononitrile were performed. The rest of the synthesis was designed theoretically, including the formation of terminal acetylene, Sonogashira coupling to bromoacetophenone, DAST fluorination and Knoevenagel condensation, introducing the final malononitrile.

• Keywords: molecular probe, metabolites, synthesis, Sonogashira coupling