Sinteza zaviralcev butirilholinesteraze iz heterocikličnih α-aminokislin

Gorenc, Ana (author), Grošelj, Uroš (mentor)

Pripravila sem diamin, 4-(2-((2-cikloheptiletil)amino)etil)-N,N-dimetilcikloheksan-1-amin, s sekundarno in terciarno aminsko skupino. Diamin sem uporabila za amidiranje Nα-(terc-butoksikarbonil)-Nα-butil-D-triptofana in 3-(1H-indol-3-il)propanojske kisline po aktivaciji s CDI. N-Boc zaščiten triptofan sem neuspešno amidirala z N-(2-cikloheptiletil)-3-(1H-indol-3-il)propan-1-aminom. Po redukciji karbonilnih skupin amida in ciklizaciji/redukciji enega izmed produktov sem dobila končne produkte, ki sem jih izolirala s kolonsko kromatografijo in v celoti okarakterizirala. Uspešno sem pripravila tri razvejene, z sp3-hibridiziranimi atomi bogate produkte z dvema aminskima skupinama in prisotno indolilno skupino. Produktom, ki so potencialni inhibitorji butirilholinesteraze v možganih, smo testirali inhibitorne sposobnosti. Pri tem smo preverili tudi specifičnost inhibicije.

• Language: Slovenian
• Keywords: heterociklične α-aminokisline, indol, amin, inhibitor butirilholinesteraze
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2019
• PID: 20.500.12556/RUL-108954
• COBISS.SI-ID: 1538294467
• Publication date in RUL: 12.08.2019

Secondary language

• Language: English
• Title: Synthesis of butyrylcholinesterase inhibitors from heterocyclic α-amino acids

Abstract

Diamine, 4-(2-((2-cycloheptylethyl)amino)ethyl)-N,N-dimethylcyclohexan-1-amine, was prepared. It contains one secondary and one tertiary amino group. The diamine was used for the amidation of Nα-(tert-butoxycarbonyl)-Nα-butyl-D-tryptophan and 3-(1H-indol-3-yl)propanoic acid after the activation of the carboxy group with CDI. N-Boc protected tryptophan was unsuccessfully amidated with N-(2-cycloheptylethyl)-3-(1H-indol-3-yl)propan-1-amine. Subsequently, amides were reduced to amines and one of the products was further cyclized/reduced. The final products were isolated with column chromatography and fully characterized. Three branched and sp3-rich final products, containing two amino groups and an indole ring, were prepared. Products which were expected to reduce levels of butyrylcholinesterase in the brain were tested for the extent of butyrylcholinesterase inhibition. Specificity of enzyme inhibition was also examined.

• Keywords: heterocyclic α-amino acids, indole, amine, butyrylcholinesterase inhibitor