(C) 2001 Published by Elsevier Science Ltd. The 6-O-acetyl group in the glycosyl donor, 6-O-acetyl-1,2-anhydro-3,4-di-O-brnzyl-alpha -D-glucopyranose did not influence the stereoselectivity of the ring-opening-coupling, reaction. Condensation of 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl-alpha -D-glucopyranose and 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl-beta -D-mannpfuranose with 1,2:3,4-di-O-isopropylidene-alpha -D-galactopyranose in the presence of ZnCl2 as the catalyst afforded the 1,2-trans-linked 6-O-acetyl-3,4-di-O-benzyl-alpha -D-glucopyranosyl-(1-6)-1,2:3,4-di-O-isopropylidene-alpha -D-galactopyranose and 5-O-acetyl-3,6-di-O-benzyl-alpha -O-mannofuranosyl-(1->6)-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose as the sole products in satisfactory yields, while condensation of 5-O-acetyl-1,2-anhydro-3-O-benzyl-beta -D-lyxofuranose with 3-O-benzyl-1,2-O-isoproyylidene-alpha -D-xylofuranose yielded the 1,2-trans-linked 5-O-acetyl-3-O-benzyl-alpha -D-lyxofuranosyl-(1->5)-3-O-benzyl-1,3-O-isopropylidene-alpha -D-xylofuranose as the sole product in a good yield. Acetyl and benzoyl groups were not affected in the ring closure reactions. These studies indicate that MRPP and ARPP inhibit PRPP synthetase, and that PRPP synthetase may be a viable target in the development of certain antitumor agents.The title compounds 5-O-acetyl-1,2-anhydro-3-O-benzyl-alpha -D-ribofuranose and 5-O-acetyl-1,2-anhydro-3-O-benzyl-beta -D-lyxofuranose, and 6-O-acetyl-1,2-auhydro-3,4-di-O-benzyl-alpha -D-glucopyranose and 6-O-acetyl-1,2-anhydro-3,4-diO-benzyl-beta -D-taloypranose, and 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl-beta -D-mannofuranose and 1,2-anhydro-5,6-di-O-benzoyl-3-O-benzyl-beta -D-mannofuranose have each been synthesized from the corresponding 2-O-tosylate and 1-free hydroxyl inter-mediates by base-initiated intramolecular S(N)2 ring closure in almost quantitative yields. In vivo treatment of BDF1 mice with a single dose of ARPP (173 mg/kg) or MRPP (62 mg/kg) extended the mean life span of the mice, which had been inoculated intraperitoneally 1 day earlier with 1 x 10(6) L1210 murine leukemia cells, by 62 and 82% respectively. When the capacity of the treated cells for sustained synthesis of PRPP was examined by adenine incorporation, the rate of adenine uptake was inhibited by greater than 50%. Treatment of cells with these agents caused a 50% reduction in the steady-state level of PRPP. For instance, 1,2,3,6-tetra-O-acetyl-alpha-D-glucopyranose was easily synthesised in good overall yield (70) starting from 1,2,3,4,6-penta-O-acetyl-alpha-D-glucopyranose by regioselective. It has a role as a human metabolite and a Saccharomyces cerevisiae metabolite. The rate of salvage of hypoxanthine to form IMP was decreased by 85%. Alpha-D-ribose 1-phosphate (2-) is dianion of alpha-D-ribose 1-phosphate arising from deprotonation of both phosphate OH groups major species at pH 7.3. Consequently, ARPP and MRPP treatment of WI-L2 cultures rapidly inhibited both de novo pyrimidine and purine synthesis as well as the nucleotide salvage reactions dependent on PRPP, ARPP or MRPP treatment completely prevented bicarbonate incorporation into acid-soluble pyrimidine and purine nucleotides. MRPP-5'-monophosphate was a competitive inhibitor (Ki = 40 microM) of the activation of this enzyme by the cofactor inorganic phosphate (K alpha = 2.2 mM). The primary target of these nucleosides appeared to be 5-phospho-alpha-D-ribofuranose-1-pyrophosphate (PRPP) synthetase. The basis for the antitumor activities of the exocyclic amino nucleosides 4-amino-(ARPP) and 4-methoxy-8-(D-ribofuranosylamino)pyrimidopyrimidine (MRPP) was investigated.

Alpha d ribofuranose