A New, Efficient Entry to Non-Lipophilic H-Phosphonate Monoesters – Preparation of Anti-HIV Nucleotide Analogues

Aryl H-Phosphonates 18. Synthesis, properties, and biological activity of 2′,3′-dideoxynucleoside (N-heteroaryl)phosphoramidates of increased lipophilicity

“…H-Phosphonates of ddU (1b), d4T (1c), ABC (1d), and 3TC (1e) were prepared by a slightly modified diphenyl Hphosphonate procedure [12]. A nucleoside (1 mmol Analytical data were in agreement with the literature [32]. …”

“…AZT H-phosphonate 1a was obtained as described previously [32]. H-Phosphonates of ddU (1b), d4T (1c), ABC (1d), and 3TC (1e) were prepared by a slightly modified diphenyl Hphosphonate procedure [12].…”

H-Phosphonate Chemistry in the Synthesis of Electrically Neutral and Charged Antiviral and Anticancer Pronucleotides

“…Alkyl or aryl ester groups in these compounds are good leaving groups that may be substituted with one or two molecules of an alcohol. There are also 2-cyanoethyl (Venijaminova et al, 1994) or 9fluorenemethyl H-phosphonates (Yang et al, 1995;Romanowska et al, 2009a) that are not reactive as such but may be activated, e.g., with pivaloyl chloride (PvCl), and effectively phosphonylate nucleoside OH function and produce the respective alkyl nucleoside H-phosphonate diesters. From these, upon treatment with tertiary amines in anhydrous conditions, the 2-cyanoethylor 9-fluorenemethyl groups can be removed quantitatively via βelimination to furnish the respective H-phosphonate monoesters.…”

“…During our studies on nucleoside H-phosphonates and their analogs, the most synthetically useful, although for different reasons, were pyro-H-phosphonate 1,9-florenemethyl H-phosphonate (Romanowska et al, 2009a) 2, and diphenyl H-phosphonate (Jankowska et al, 1994) 3 (Figure 1).…”

“…Pyro-H-phosphonate 1 was particularly useful in the synthesis of another type of phosphonylating reagent, 9-fluorenemethyl H-phosphonate 2 (Yang et al, 1995;Romanowska et al, 2009a) Typically, it is obtained in the reaction of 9-fluorenemethanol and an excess (3 molar equiv.) of pyro-H-phosphonate in pyridine.…”