Naslov
Synthesis, structural studies, and cytostatic evaluation of 5,6-di-O-modified L-ascorbic acid derivatives

Autori
Gazivoda, Tatjana ; Wittine, Karlo ; Lovrić, Iva ; Makuc, Damjan ; Plavec, Janez ; Cetina, Mario ; Mrvoš-Sermek, Draginja ; Šuman, Lidija ; Kralj, Marijeta ; Pavelić, Krešimir ; Mintas, Mladen ; Raić-Malić, Silvana

Izvornik
Carbohydrate research (0008-6215) 341 (2006), 4; 433-442

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
L-ascorbic acid ; configurational analysis ; conformational analysis ; single crystal X-ray diffraction ; cytostatic activity

Sažetak
The 5, 6-di-O-tosylated derivative of L-ascorbic acid was synthesized by selective protection and deprotection of 2, 3- and 5, 6-dihydroxy functional groups involving 5, 6-ditosylation in the final step, while the novel 6-acetoxy, 6-hydroxy and 6-chloro derivatives of 4, 5-didehydro-L-ascorbic acid were obtained by reaction of ditosylated compound with nucleophilic reagents. The analysis of 3JH4H5 homonuclear coupling constants shows that all L-ascorbic acid derivatives except for epoxy and 4, 5-didehydro compounds exist in high population as gauche conformers across C-4--C-5 bonds, while 3JC3H5 heteronuclear coupling constants in 4, 5-didehydro derivatives indicate cis geometry along C-4--C-5 double bond. The X-ray crystal structure analysis of 2, 3-di-O-benzyl-5, 6-epoxy- and 5, 6-isopropylidene-L-ascorbic acid shows that the oxygen atoms attached at positions 2 and 3 of the lactone ring are disposed in a synperiplanar fashion. Besides that, the dioxolane ring adopts half-chair conformation. The molecules of epoxy derivative are joined into infinite chains by one weak hydrogen bond of C-H• • • O type. Two O-H• • • O and C-H• • • O hydrogen bonds link the molecules of 5, 6-isopropylidene compound into two-dimensional network. 6-Chloro derivative of 2, 3-di-O-benzyl-L-ascorbic acid showed the best cytostatic effects against all tested malignant tumor cells (IC50: ~18 uM).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA