5-(trifluoromethyl)-beta-L-2 '-deoxyuridine, the L-enantiomer of trifluorothymidine: Stereospecific synthesis and antiherpetic evaluations

As a part or our ongoing work on beta -L-nucleoside analogues as potential antiviral drugs. we have synthesized 5-(trifluoromethyl)-beta -L-2'-deoxyur idine (L-TFT), the hitherto unknown L-enantiomer of trifluorothymidine (CF( 3)dUrd, TFT). We have also studied the effect of L-TFT on human and herpes simplex virus (HSV) type 1 and 2 thymidine kinases, and human thymidine pho sphorylase. as well as its anti-HSV-1 and anti-HSV-2 activities in cell cul tures. L-TFT has been found: (i) to inhibit HSV-I TK with activity comparab le to TFT, with no effect on human TK. (ii) to be phosphorylated by the vir al enzyme with similar efficiency to TFT. (iii) to be resistant, in contras t to TFT. to hydrolysis by human thymidine phosphorylase. Unfortunately. wh en evaluated in cell cultures, L-TFT did not show any anti-HSV-1 and anti-H SV-1 activities. (C) 2001 Elsevier Science Ltd. All rights reserved.