102219-52-3Relevant academic research and scientific papers
2-(4-Nitrophenyl)ethyl Methylenebis(phosphonate): A Versatile Reagent for the Synthesis of Nucleoside 5′-Methylenebis(phosphonate)s
Lesiak, Krystyna,Watanabe, Kyoichi A.,George, Jay,Pankiewicz, Krzysztof W.
, p. 1906 - 1909 (1998)
2-(4-Nitrophenyl)ethyl methylenebis(phosphonate) (6) was prepared by reaction of equimolar amounts of 2-(4-nitrophenyl)ethyl alcohol and methylenebis(phosphonyl) tetrachloride in the presence of tetrazole. Compound 6 was further converted into the corresponding 4-nitrophenylethyl trisanhydride intermediate 7 by dehydration with diisopropylcarbodiimide (DIC). Reaction of 7 with either 2′,3′-O-isopropylideneadenosine (8a) or 2′,3′-O-isopropylideneguanosine (8b) afforded, after hydrolysis, the desired P 1-[2-(4-nitrophenyl)ethyl]-F2-(2′,3′-O- isopropylideneadenosin-5′-yl) methylenebis(phosphonate) (9a) and guanosine analogue 9b, respectively. A similar treatment of intermediate 7 with 3′-O-acetylthymidine (12a), 3′-O-acetyl-2′-deoxy-N4-benzoylcytidine (12b), 3′O-acetyl-2′-deoxy-N6-benzoyladenosine (12c), and 3′-O-acetyl-2′-deoxy-N2-isobutyrylguanosine (12d) gave the corresponding 2-(4-nitrophenyl)ethyl methylenebis(phosphonate)s 13a-d. These compounds as well as 9a,b were treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) which caused elimination of the 2-(4-nitrophenyl)ethyl group. The base labile 3′-O-acetyl, N4-acetyl, N6-benzoyl, and N2-isobutyryl groups of 12a-d were also removed during the DBU treatment. Thus, the 5′methylenebis(phosphonate)s of 2′,3′-O-isopropylideneadenosine (10a), 2′,3′-O-isopropylideneguanosine (10b), thymidine (14a), 2′-deoxycytidine (14b), 2′-deoxyadenosine (14c), and 2′deoxyguanosine (14d) were prepared in good yield. De-O-isopropylidenation of 10a and 10b afforded adenosine 5′-methylenebis(phosphonate) (11a) and guanosine 5′-methylenebis(phosphonate) (11b), respectively.
Conversion of adenine to 5-amino-4-pyrimidinylimidazole caused by acetyl capping during solid phase oligonucleotide synthesis
Rodriguez, Andrew A.,Cedillo, Isaiah,McPherson, Andrew K.
, p. 3468 - 3471 (2016)
The acetyl capping reaction used throughout solid phase oligonucleotide synthesis is meant to minimize n?1 deletionmer impurities by terminating sequences that fail to couple to a phosphoramidite. However, the reaction is also responsible for the formatio
Synthesis and biological evaluation of triazolyl 13α-estrone-nucleoside bioconjugates
Bodnár, Brigitta,Mernyák, Erzsébet,W?lfling, János,Schneider, Gyula,Herman, Bianka Edina,Szécsi, Mihály,Sinka, Izabella,Zupkó, István,Kupihár, Zoltán,Kovács, Lajos
, (2016/09/23)
2' -Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne-azide click reaction (CuAAC). For the introduction of the azido group the 5? -position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3? -hydroxy groups of the nucleosides were protected by acetyl groups and the 5? -hydroxy groups were modified by the tosyl-azide exchange method. The commonly used conditions for click reaction between the protected-5? -azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I) catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780) and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC50 value of 9 μM). The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC50 = 19 μM).
