Phosphorus hemiacetal activation

The 2, 3 -dideoxy-3 -C-(phosphonomethyl)nucleosides (38) of the five common nucleotide bases have been prepared by a condensation of the nucleobases with 1,2-di-O-acetyl-S-O-benzoyl-3-deoxy-3-(methoxyphosphorylmethyl)-6-D-ribofuranose (39). Conversion to the deoxyribose derivative was accomplished by reduction of the 2 -thionocarlKHUite and hydrolysis of the phosphonic ester groups using bromotrimethylsilane. 9-(l-Deoxy-l-phosphono-B-D-p(5CO-furanosyl)-l,9-dihydro-67f-purin-6-one (40, Scheme 4) has been prepared as a potential transition state inhibitor of purine nucleoside phosphorylase. The crucial step in the synthesis involved the carixm-phosphorus bond formation by reaction of the hemiacetal (41) with triethyl-phosphite. Nucleotide (40) proved to be very susceptible to hydrolysis of the glycosidic bond (half-life of thirty-nine minutes, pH 7), but showed weak inhibitory activity (K- = 26 /iM) against purine nucleoside phosphorylase. 

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