The New C-5 Substituted Uracil Derivatives of 4, 5-didehydro-5, 6-dideoxy-L-Ascorbic Acid: Synthesis, Antitumoral and Antiviral Evaluations

We have found in our previous studies that some pyrimidine and purine derivatives of 4, 5-didehydro-5, 6-dideoxy-L-ascorbic acid possess pronounced cytostatic activities against some malignant human tumor cell lines [1]. In this connection we have synthesized a series of novel C-5 pyrimidine derivatives of 2, 3-di-O-benzyl-4, 5-didehydro-5, 6-dideoxy-L-ascorbic acid (Figure) by Stille reaction of the 5-iodouracil derivative of L-ascorbic acid with unsaturated stannanes. The novel compunds were evaluated for their cytostatic activities against malignant human tumor cell lines: pancreatic carcinoma, cervical carcinoma, breast carcinoma, laryngeal carcinoma, colon carcinoma, human T-lymphocytes, as well as human fibroblast cells. Inhibitory activity evaluations of those compounds against herpes simplex virus type 1 and 2, vaccinia virus, variccela-zoster virus, vesicular stomatitis virus, Coxsackie virus B4, respiratory syncytial virus, parainfluenza virus, reovirus-1, sindbis virus and Punta Toro virus were also performed. The results of antitumoral and antiviral evaluations will be presented. [1] (a) T. Gazivoda et al, Carbohydrate Res. 2006 (341) 433 ; (b) T. Gazivoda et al, Bioorg. Med. Chem. 2005 (13) 131 ; (c) S. Raic-Malic et al, J. Med. Chem. 2000 (43) 4806 ; (d) S. Raic-Malic et al, J. Med. Chem. 1999 (42) 2673.