Synthesis of Functionalized Diethyl(pyrrolidin-2-yl)phosphonate and Diethyl(5-oxopyrrolidin-2-yl)phosphonate.

Short and efficient syntheses of functionalized (pyrrolidin-2-yl)phosphonate and (5-oxopyrrolidin-2-yl)phosphonate have been developed. The synthetic strategy involved the diastereospecific 1,3-dipolar cycloaddition of -benzyl--(diethoxyphosphoryl)nitrone to -1,4-dihydroxybut-2-ene and dimethyl maleate, respectively. ,-Diethyl 3-carbamoyl-4-hydroxy(5-oxopyrrolidin-2-yl)phosphonate was obtained from ,-diethyl 2-benzyl-4,5-dimethoxycarbonyl(isoxazolidin-3-yl)phosphonate by hydrogenation and subsequent treatment with ammonia, whereas transformation of ,-diethyl 2-benzyl-4,5-dihydroxymethyl(isoxazolidin-3-yl)phosphonate into ,-diethyl 3-aminomethyl-4-hydroxy(pyrrolidin-2-yl)phosphonate was accomplished by mesylation followed by hydrogenolysis to undergo intramolecular cyclization and the introduction of amino group via ammonolysis.

Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-]pyridine, imidazo[4,5-]pyridine and imidazo[4,5-]pyridin-2(3)-one systems.

A new series of phosphonylated triazolo[4,5-]pyridine (1-deaza-8-azapurine), imidazo[4,5-]pyridine (1-deazapurine) and imidazo[4,5-]pyridin-2(3)-one (1-deazapurin-8-one) were synthesized from 2-chloro-3-nitropyridine and selected diethyl ɷ-aminoalkylphosphonates followed by reduction of the nitro group and cyclization. In the final step ,-diethylphosphonates were transformed into the corresponding phosphonic acids. All synthesized compounds were evaluated for inhibitory activity against a broad variety of DNA and RNA viruses and their cytotoxic potencies were also established.