- Oxidation-reduction sequence for the synthesis of peracylated fluorodeoxy pentofuranosides
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The oxidation of methyl 5-O-benzyl-3(2)-deoxy-3(2)-fluoro-α-D-pentofuranosides with dimethyl sulfoxide-acetic (trifluoroacetic) anhydride was accompanied by epimerization at the carbon atom bearing a fluoro function, resulting in the formation of the corresponding 2- or 3-keto derivatives as mixtures of two epimers in high combined yield.Reduction of a mixture of the erythro/threo epimeric 2-keto sugars (isolated as stable hydrates) with sodium borohydride in benzene-ethanol proceeded stereoselectively leading to the formation of 3-deoxy-3-fluoro ribo- and lyxo-furanosides, respectively.In the case of the ribo and arabino epimers of the 3-keto sugar (isolated as free ketones), reduction stereoselectivity of the former was >95percent for the 2-deoxy-2-fluoro ribo sugar, whereas a ca. 3:1 lyxo/arabino ratio of products was obtained for the latter.Treatment of a mixture of the 2-epimeric 3-keto sugars with triethylamine in carbon tetrachloride at room temperature for 3-5 h afforded the 2-deoxy-2-fluoro ribo ketone (ca. 90percent).The synthesis of 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-α,β-D-lyxofuranose (8) and 1-O-acetyl-3,5-di-O-benzoyl-2-deoxy-2-fluoeo-β-D-ribofuranose (16) and their use as glycosylating agents for bis-trimethylsilylated N6-benzoyladenine is described.Keywords: Fluorodeoxy pentafuranosides; Keto sugars; Epimerization
- Mikhailopulo, Igor A.,Sivets, Grigorii G.,Poopeiko, Nicolai E.,Khripach, Natalia B.
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- Synthesis and biologic activity of purine 2'-deoxy-2'-fluoro- ribonucleosides
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The synthesis of 3,5-di-O-benzoyl-2-deoxy-2-fluoro-D-ribofuranosyl bromide (8) and its reaction with 2,6-dichloropurine by fusion and with mercuric cyanide catalysis is described. The resulting 2,6-dichloro-9-(3,5-di-O- benzoyl-2-deoxy-2-fluoro-β-D-ribofuranosyl)purine (13) was converted to the 2-fluoroadenine (16), the 2-chloroadenine (17), 2,6-diaminopurine (12), and guanine (14) nucleosides by standard procedures. These nucleosides were cytotoxic to a number of cell lines in culture. The 2-haloadenine nucleosides 16 and 17 gave modest increases in lifespan when tested against the P388 leukemia in mice.
- Thomas,Tiwari,Clayton,Secrist III,Montgomery
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p. 309 - 323
(2007/10/02)
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