L-Ascorbic acid and its derivatives

Abstract

Cilj ovog rada bila je regioselektivna sinteza 1,4-disupstituiranih-1,2,3-triazolnih derivata L-askorbinske kiseline (6−17) kao potencijalnih antitumorskih spojeva. U tu svrhu sintetizirani su derivati L-askorbinske kiseline 1, 2, 3 i 4 koji su ključni za sintezu azida L-askorbinske kiseline 5. 1,2,3-triazolni derivati L-askorbinske kiseline pripravljeni su reakcijom 1,3-dipolarne cikoladicije s Cu(I) kao katalizatorom. S ciljem dobivanja većeg sveukupnog iskorištenja ciljanih produkata, korištena su dva sintetska puta. Prvi put predstavljao je tandemsku reakciju prevođenja tosiliranog derivata L-askorbinske 4 u azid i 'klik' kemiju azida 4 u 1,4-disupstituirane-1,2,3-triazolne derivate L-askorbinske kiseline (6−17), dok se drugim putem provodila sinteza i izolacija svih navedenih spojeva. Strukture svih sintetiziranih spojeva potvrđene su 1H- i 13C-NMR spektroskopijom.The aim of this work was the synthesis of 1,4-disubstituted 1,2,3-triazole derivatives of L-ascorbic acid (6−17) with potential antiproliferative activity using regioselective approach. For this purpose, L-ascorbic acid derivatives 1, 2, 3 and 4 required for the synthesis of L-ascorbic acid azide 5 were prepared by 1,3-dipolar cycloaddition reaction with Cu(I) as a catalyst. In order to obtain better overall yield of target compounds, two synthetic pathways were used. First pathway represented tandem reaction of tosylated L-ascorbic acid derivative 4 to azide derivative 5 and click chemistry of azide to 1,4-disubstituted 1,2,3-triazole derivatives of L-ascorbic acid (6−17), while other synthetic pathway involved synthesis and isolation of each above-mentioned product. The structures of all compounds have been confirmed by 1H- and 13C-NMR spectroscopy