Colleen A. Evans

Expeditious preparation of (−)-2′-deoxy-3′-thiacytidine (3TC)

Abstract The title compound has been prepared in enantiomerically pure form in four steps from (+)-thiolactic acid.

Oxidative degradation of L-ascorbic acid acetals to 2′,3′-dideoxy-3′-oxaribofuranosides. Synthesis of enantiomerically pure 2′,3′-dideoxy-3′-oxacytidine stereoisomers as potential antiviral agents

Abstract Enantiomerically pure 2′,3′-dideoxy-3′-oxacytidine nucleoside analogues were synthesized from L-ascorbic acid in eight steps and good overall yield.

STRUCTURE-ACTIVITY RELATIONSHIPS AMONG A NEW CLASS OF ANTIVIRAL HETEROSUBSTITUTED 2',3'-DIDEOXYNUCLEOSIDE ANALOGUES

Abstract 3′-Oxa-4′-thiocytidine nucleoside analogues 14–17 were prepared from oxathiolanes 10 and 11, and evaluated for activity against HIV-1 and HBV in vitro. The nucleoside analogues were found to possess potent activities against HIV-1 in a panel of cell lines. Compound 16 is moderately active against HBV in 2.2.15 cells.

Decarboxylative Carbon Acylation of Malonates with Aminoacylimidazolides Mediated by Lewis Acids

Abstract Various N-protected aminoacylimidazolides undergo decarboxylative carbon acylation with sodium or potassium nonomethylmalonate in THE in the presence of MgCl2, CoCl2 or MnCl2 to give dipeptide analogues (3) in 45–82% isolated yield. Amino Ketoester (3e) undergoes intramolecular cyclization induced by diisopropylethylamine and anhydrous magnesium chloride to trisubstituted tetramic acid (4).

Divergent asymmetric syntheses of dioxolane nucleoside analogues

Abstract Oxidative degradation of benzyloxymethylacetals derived from D-mannitol or L-ascorbic acid provides dioxolane intermediate 6 and 7 useful in the synthesis of all the stereoisomers of dioxolane nucleoside analogues.

Structure-Activity Relationship of Pyrimidine Heterosubstituted Nucleoside Analogues

Abstract The structure-activity relationship of sixteen 3-deaza, C-4 substituted pyrimidines and imidazo[1,2-c]pyrimidine bases of 1,3-oxathiolanes and 1,3-dioxolanes revealed good anti-HBV activity in 2.2.15 cells transfected with human hepatitis B virus of the imidazo[1,2-c]pyrimidine nucleosides 21, 25 and 29. Two procedures for the preparation of C-4 substituted analogues are reported based on nucleophilic displacement of a sulfonamide or imidazole by a variety of nitrogen nucleophiles.

Discovery of imidazo[1,2-c]pyrimidin-5(6H)-one heterosubstituted nucleoside analogues with potent activity against human hepatitis B virus in vitro

Abstract The in vitro antihepatitis B virus (HBV) activities of eleven novel imidazo[1,2-c]pyrimidin-5(6H)-one dideoxynucleoside analogues in which the sugar ring is 1,3-dioxolane or 1,3-oxathiolane were compared in the chronically HBV-producing human cell line 2.2.15. Seven nucleoside analogues 4, 9, 10, 15, 16, 18, and 24, of which 16 possesses the trans relative stereochemistry, displayed good potency and selectivity towards HBV. The order of decreasing potency at the 90% extracellular DNA inhibition level was 15>16>24≈9>10>18 . None of the tested imidazo[1,2-c]pyrimidines inhibited the replication of HIV-1 in MT-4 cells.

Unexpected effects of Lewis acids in the synthesis of optically pure 2′-deoxy-3′-oxacytidine nucleoside analogues

Abstract TiCl 4 and SnCl 4 promote the formation of dioxolane nucleosides with racemization in the coupling of enantiomerically pure 2′-deoxy-3′oxaribosides with silylated N -acetylcytosine. The use of TMSOTf, TMSI or TiCl 2 (Oi-Pr) 2 furnishes enantiomerically pure cytosine dioxolane nucleosides in low diastereoselectivity.

On The Conversion of Arabino- and Ribofuranosyl Methyl Glycosides to Their 1-O-Acetyl Derivatives

Improved conditions for the acetolysis of methyl 2,3,5-tri-O-benzyl-α-and β-L-arabinofuranosides and 2,3,5-tri-O-benzoyl-α-and β-L-ribofuranosides have been investigated. In the case of the arabino...

N-Protected α-Aminomethylketone Analogues of C-Terminal p-Nitrobenzyl-3-Ketoesters of N-Protected Amino Acids

Abstract Hydrogenolysis of N-protected amino acid p-nitrobenzyl-3-ketoesters over palladium on charcoal in THF gave N-protected α-amino methylketones in 45-83% isolated yield.