Priprava nenaravnih derivatov fenilalanina in poskus njihove vgradnje v polipeptidne verige biološko pomembnih peptidov

Angelevski, Filip (author), Gazvoda, Martin (mentor)

Sintetiziral sem polijodirane derivate L-fenilalanina ter N-Fmoc-3,4-dijodofenilalanin iz naravne aminokisline z namenom njihove nadaljnje pretvorbe v poliboronirane različice L-fenilalanina. Le-te bi lahko nadalje preko SPPS metod vključil v polipeptidne verige. Izhodni L-fenilalanin sem jodiral z elektrofilno aromatsko substitucijo s kalijevim jodatom in elementarnim jodom v močno kislem mediju, po reakciji sem s flash kolonsko kromatografijo ločil dijodirane in trijodirane produkte. Na surov produkt sem nato uvedel Fmoc zaščitno skupino v mešanem organsko-vodnem mediju z N-(9H-fluorenilmetoksikarboniloksi) sukicinimidom . Dijodiran produkt sem uspešno očistil z normalno-fazno kolonsko kromatografijo. O sintentiziranih spojinah do sedaj ni bilo poročil v literaturi. Prav tako sem sintetiziral N-Fmoc-L-4-boronofenilalanin iz čistega L-4-boronofenilalanina z uporabo (9H-fluorenil)metilnega estra kloroformatne kisline, ter skušal pripraviti nativni človeški inzulin iz polipeptidnih verig, ki sem jih sintetiziral preko SPPS.

• Language: Slovenian
• Keywords: L-fenilalanin, SPPS, jodiranje, Fmoc zaščita, inzulin
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2025
• PID: 20.500.12556/RUL-170476
• COBISS.SI-ID: 243715331
• Publication date in RUL: 07.07.2025

Secondary language

• Language: English
• Title: Synthesis of unnatural phenylalanine derivatives and their incorporoation into biologically relevant peptides

Abstract

I synthesized polyiodinated derivatives of L-phenylalanine, as well as N-Fmoc-3,4-diiodophenylalanine from the natural amino acid. I intended to further convert these compounds into their respective polyboronated derivatives, which I intended to introduce into polypeptide chains via SPPS. I used L-phenylalanine as the starting material which I iodinated via electrophilic aromatic substitution with potassium iodate and elemental iodine under strongly acidic conditions. Thereafter I used flash column chromatography to separate the di- and triiodinated products. I introduced the Fmoc protecting group to the crude product through a reaction in a mixed aqueous-organic medium with the use of N-(9-fluorenylmethoxycarbonyloxy) succinimide. The diiodinated product was then isolated with normal-phase column chromatography. The synthesized compounds haven’t been reported in literature yet. I also synthesized N-Fmoc-L-4-boronophenylalanine from pure L-4-boronophenylalanine with the use of the (9H-fluorenyl)methyl ester of chloroformic acid. I also attempted the synthesis of native human insulin from independently prepared polypeptide chains that I obtained through SPPS.

• Keywords: L-phenylalanine, SPPS, iodination, Fmoc protection, insulin