Nicolai E. Poopeiko

Oxidation-reduction sequence for the synthesis of peracylated fluorodeoxy pentofuranosides☆

Abstract 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 > 95% 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. 90%). 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-fluoro -β- d - ribofuranose (16) and their use as glycosylating agents for bis-trimethylsilylated N6-benzoyladenine is described.

xylo-Configured Oligonucleotides (XNA, Xylo Nucleic Acids): Synthesis and Hybridization Studies

Abstract We report synthesis and high-affinity hybridization of fully modified home-thymine 2′-deoxy and 2′-deoxy-2′-fluoro xylo nucleic acids.

Synthesis and Biological Properties of 2-Amino-3-fluoro-2,3-Dideoxy-D-Pentofuranosides of Natural Heterocyclic Bases

Abstract The oxidation of methyl 5–0-benzyl-3-deoxy-3-fluoro-α-D-arabi-nofuranoside (1) with DMSO/Ac2o afforded a ∼ 2:1 mixture of 2-keto derivatives with erythro and threo configuration resulting from isomerization at C3. Successive treatment of the above mixture with MeONH2, LiA1H4, and S-ethyl trifluoroacetate followed by silica gel chromatography afforded methyl 5–0-benzyl-2, 3-dideoxy-3-fluoro-2-(trifluoroacetamido)-α-D-ribofuranoside (6b) and its lyxo isomer 7b in a total yield of 25% and 5%, respectively. The arabino analogue 25 was prepared from 6b. Compounds 6b, 7b and 25 were converted to the corresponding 5–0-benzoyl derivatives 8a, 9 and 26. A series of 2′-amino-2′, 3′-dideoxy-3′-fluoro-β-D-ribo- and-α-D-lyxofuranosides of natural heterocyclic bases have been synthesized starting from 8a and 9. None of the test compounds had any antiviral activity. 3′-Fluoro-2′-amino-2′, 3′-dideoxycytidine (16) was the only compound showing inhibition of murine L1210 and human Molt/4F cell proliferation (50% e...

Synthesis and Biological Evaluation of 2′,3′-Dideoxy-3′-Fluororibofuranosyl Purine Nucleosides

Synthesis of 9-(2,3-dideoxy-3-fluoro-beta-D-ribofuranosyl)-2-chloroadenine (7b) and -2-chloro-6-methoxypurine (9b), as well as the alpha-D-anomer 7a of the former and its N-7 isomer 10a is reported. Among the compounds synthesized, only the beta-D-anomer 7b displays moderate cytotoxic activity.

OXIDATION-REDUCTION SEQUENCE FOR THE SYNTHESIS OF PERACYLATED FLUORODEOXY PENTOFURANOSIDES

Abstract Oxidation of 1a with DMSO-acetic or trifluoroacetic anhydride led to the formation of a mixture of epimeric gem-diols 2 and 3 in the ratios of ≍3:1 and ≍7:1, respectively. Reduction of this mixture with NaBH4 followed by benzoylation and chromatography afforded 4a and 5a.

Epimerization at C2 of Methyl 5-O-Benzyl-2-deoxy-2-fluoro-α-D-pentofuranosides upon Oxidation

Abstract Oxidation of 1 with DMSO-acetic anhydride resulted in the formation of a mixture of epimeric ketones 2 and 3 in the ratio of ≍3:1 in high combined yield. Acetolysis of methyl glycoside 5 afforded 1-O-acetyl-3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-ribofuranoside (6)(83%). The latter was reacted with silylated N6-benzoyladenine to give α- and β-ribosides (1:3.7; 61%, combined).