University of Zagreb. Faculty of Chemical Engineering and Technology.
Abstract
Cilj ovog rada bila je regioselektivna sinteza 1,4-disupstituiranih 1,2,3-triazolnih derivata L-askorbinske kiseline (3 – 8) kao potencijalnih antitumorskih spojeva. U tu svrhu sintetizirana je 6-O-tosil-2,3-O,O-dibenzil-L-askorbinska kiselina (1) koja je potom prevedena u odgovarajući azidni derivat L-askorbinske kiseline (2). 1,2,3-triazolni derivati L-askorbinske kiseline (3 – 8) pripravljeni su reakcijom 1,3-dipolarne cikoladicije azida (2) i odgovarajućih terminalnih alkina potpomognutom mikrovalnim zračenjem s Cu(I), kao katalizatorom, prema konceptu "klik" kemije. S ciljem dobivanja većeg sveukupnog iskorištenja reakcija kojima nastaju ciljani produkti korištena su dva sintetska puta. Prvi sintetski put uključuje reakciju prevođenja tosilatnog derivata L-askorbinske (1) u azid (2) i njegovu izolaciju te potom "klik" reakciju azida (2) i odgovarajućih alkina u 1,4-disupstituirane 1,2,3-triazolne derivate L-askorbinske kiseline (3 – 8). Drugi sintetski put je bila tandemska reakcija u kojoj se azid (2) nije izolirao nego je nastao in situ iz tosilatnog derivata (1) i reakcijom s odgovarajućim alkinima dobiveni su 1,4-disupstituirani 1,2,3-triazolni derivati L-askorbinske kiseline (3, 5). Kako bi se ispitalo antioksidativno djelovanje 1,4-disupstituiranih 1,2,3-triazolnih derivata L-askorbinske kiseline, uklanjanjem benzilne zaštite priređen je spoj 9 sa slobodnih hidroksilnim skupinama. Strukture svih sintetiziranih spojeva potvrđene su spektroskopijom 1H i 13C NMR.The aim of this work was the regioselective synthesis of 1,4-disubstituted 1,2,3-triazole L-ascorbic acid derivatives (3 – 8) with potential antitumor activity. For this purpose, 6-O-tosyl-2,3-O,O-dibenzyl-L-ascorbic acid (1) was prepared and then converted to the corresponding azido derivative of L-ascorbic acid (2). 1,2,3-Triazole derivatives of L-ascorbic acid (3 – 8) were prepared by microwave assisted 1,3-dipolar cycloaddition reaction of the azide (2) and corresponding terminal alkynes with Cu(I), as a catalyst, based on the concept of "click" chemistry. In order to obtain better overall yield of target compounds, two synthetic pathways were used. First pathway includes the conversion of the tosylated L-ascorbic acid derivative (1) to the azide (2), its isolation and then a "click" reaction of the azide (2) and corresponding alkynes to form 1,4-disubstituted 1,2,3-triazole L-ascorbic acid derivatives (3 – 8). Second synthetic pathway was a tandem reaction in which the azido derivative (2) was not isolated, but was formed in situ from the tosylated derivative (1) and via reaction with the corresponding alkynes 1,4-disubstituted 1,2,3-triazole derivatives of L-ascorbic acid (3, 5) were obtained. In order to explore the antioxidant properties of the 1,2,3-triazole L-ascorbic acid derivatives, compound with free hydroxyl groups (9) was prepared by removal of the benzyl protecting groups. The structures of all compounds have been confirmed by 1H and 13C NMR spectroscopy
