Synthesis and Antitumor Activity of 7- and 9-(6′-Deoxy-α-L-talofuranosyl)hypoxanthine and 9-(6′-Deoxy-α-L-talofuranosyl)-6-thiopurine

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Reaction of 6-deoxy-2,3,5-tris-O-(p-nitrobenzoyl)-L-talofuranosyl bromide (1) with the trimethylsilyl derivative of hypoxanthine, followed by removal of blocking groups, afforded 9- (6) and 7-(6′-deoxy-α-L-talofuranosyl)hypoxanthine (7). A study of the published optical rotations and circular dichroic (CD) spectra of pentofuranosylpurines and of (6′-deoxy-β-D-allo- and -α-L-talofuranosyl)purines prepared here suggests that the sign of rotation and the sign of the longer wavelength Cotton effect is determined solely by the configuration of C-1’ and its position of attachment to the purine ring. For C-1’ R nucleosides, the sign is negative for N-9-linked purine nucleosides and positive for the N-7-linked isomers, and vice versa for C-1'S purine nucleosides. Reaction of 1 with the trimethylsilyl derivative of 6-chloropurine afforded 4, which upon treatment with thiourea and deblocking yielded 9-(6′-deoxy-o!-L-talo-furanosyl)-6-thiopurine (8). Unlike the previously prepared 7-(6′-deoxy-β-D-allofuranosyl)hypoxanthine which strongly inhibited purine nucleoside phosphorylase, compounds 6-8 did not inhibit this enzyme. Compound 8 significantly inhibited the growth of L1210 tumor cells in vitro and in vivo. © 1983, American Chemical Society. All rights reserved.

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Journal of Medicinal Chemistry