Ja. Secrist et al., SYNTHESIS AND BIOLOGICAL-ACTIVITY OF CERTAIN 4'-THIO-D-ARABINOFURANOSYLPURINE NUCLEOSIDES, Journal of medicinal chemistry, 41(20), 1998, pp. 3865-3871
A series of 4'-thio-n-arabinofuranosylpurine nucleosides was prepared
and evaluated as potential anticancer agents. The details of a conveni
ent and high-yielding synthesis of the carbohydrate precursor acetyl-2
,3,5-tri-O-benzyl-4-thio-D-arabinofuranose (6) are presented. Proof of
structure and configuration at all chiral centers of the nucleosides
was obtained through an X-ray crystal structure of 9 alpha as well as
through NOE experiments on 9 beta and 9 alpha. All six target compound
s were evaluated in a series of human cancer cell lines in culture. Tw
o target compounds, beta anomers with diaminopurine (12) and guanine (
16) as the bases, had significant cytotoxicity. One of these compounds
(12) was selected for animal studies but was found to have no selecti
vity at the maximum tolerated dose in the murine colon 36 tumor model.