Synthesis of Novel 4′-Trifluoromethyl-5′-NorcarbocyclicC-Nucleoside Phosphonic Acids as Potent Anti-Leukemic Agents

Abstract

The syntheses of novel C-nucleoside phosphonic acids as potential antiviral agents are described. The sugar moiety that served as the nucleoside skeleton was produced starting from commercially available 1,3-dihydroxy cyclopentane. The key C-C bond formation from sugar to base precursor was performed using the Knoevenagel-type condensation. The synthesized compounds exhibited anti-HIV activity and cytotoxicity. Also, the synthesized compounds were screened in vitro for tumor growth inhibitory activity against mouse leukemia cell lines (L-1210, P-815).

Approaches to the synthesis of heterocyclic C-nucleosides

“…4´-Trifl uoromethylated carbocyclic nucleoside 266 was synthesized similarly via intermediate 265 (Scheme 86). 99 The yield of nucleoside 266 was 1.7% over seven steps.…”

Expanding Heteroaromatic and 2-Aminosugar Chemical Space Accessible from the Biopolymer Chitin

“…One target that fulfils these criteria is furo [3,2-d]pyrimidin-4-amine 1, a heteroaromatic scaffold found in the C-nucleoside antibiotic pyrrolosine [26][27][28] and employed in a multitude of medicinal chemistry programmes against a diverse range of targets, including spleen tyrosine kinases [29], G protein-coupled receptor 119 [30], p110δ PI3 kinase [31], and FYVE-type finger-containing phosphoinositide kinases [32]. We envisaged that the heteroaromatic ring system 1 could be accessible from 3A5AF via cyanation at C2 followed by acetamide hydrolysis to provide aminonitrile 2 followed by heteroannulation with formamidine [27,28,33,34] (Scheme 2). Although only one nitrogen atom in 1 is sourced from chitin, our aim was to source other N-atoms from N-compounds present in nature (q.v).…”