ChemInform Abstract: Synthesis of Non‐Glucoside Analogues of 6‐Azacytidine and 6‐Azauridine

Abstract

Synthesis of Non-Glucoside Analogues of 6-Azacytidine and 6-Azauridine -(such as (II) based on the oxidative cleavage of the carbohydrate moiety of corresponding nucleosides). -(OGNYANIK, S. S.; SHALAMAI, A. S.; ALEKSEEVA, I. V.; LYSENKO, N. A.; Ukr. Khim. Zh. (Russ. Ed.) 61 (1995) 5-6, 52-55; Inst. mol., biol. genet. Nats. Akad. nauk Ukr., Kiev, Ukraine; UK)

Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues

“…It should be noted that ribavirin (18) and cidofovir (19) reference compounds studied under the same experimental conditions appeared to be much weaker AdV inhibitors (EC 50 33 and 10.7 μM, respectively) than 6-azaCyd.…”

“…[9] Chemical shifts of anomeric protons and J 1'-2' coupling constants of rhamno-and arabinopyranosyl derivatives 11-15 are close to those of previously reported glucopyranosyl analogues. [11] Note that the NMR spectra of free nucleosides 12, 15, as well as seco-nucleoside 9, show the doublet splitting of exo-NH 2 group signal characteristic for 6-azacytidine ( δ 0.11-0.12 ppm), which is most pronounced in compounds 9a [19] and 17 ( δ 0.55 and 0.39 ppm, respectively). The non-equivalence of amino group protons results from its restricted rotation and the asymmetry of 1,2,4-triazinyl heterocycle electronic structure, which is enhanced by the introduction of substituents at C-3 and/or C-6 positions of the ring.…”

“…followed by the reduction of thus generated aldehyde groups by sodium borohydride as reported previously. [18,19] The structures of the obtained compounds were confirmed by spectral data ( 1 H NMR, UV, and MS) and their comparison with the spectra of 6-azacytidine and its derivatives with known structure. [9,11] Thus, the position of anomeric proton of exo N-monosubstituted β-D-ribofuranosyl derivatives 2-6 (δ 5.94-5.96 ppm with a coupling constant value of 3.6-4.0 Hz) and their λ max (266-272 nm) is in agreement with reported data.…”

“…[20] This interpretation is consistent with quantum-chemical [18] (e) NaIO 4 , then NaBH 4 . [19] characteristics of 6-azacytidine. This nucleoside exhibits a high dipole moment and can actively participate in the formation of hydrogen bonds and dipole-dipole and π -stacking interactions.…”

“…UV (H 2 О): λ max 265 nm (lg ε 4.06). 1 H NMR: δ 11.50 (s, 1H, NH), 8.72 (s, 1H, C5H), 6.21 (d, 1H, 1 -H, J = 3.2 Hz), 5.58 (t, 1H, 2 -H, J = 3.5 Hz), 5.40 (t, 1H, 3 -H, J = 5.6 Hz), 4.32 (m, 2H, 4'-H, 5'-H), 4.06 (dd, 1H, 5'-H, J = 4.4 Hz), 2.18 (s, 3H, Ac), 2.08 (2s, 6H, 2Ac), 2.02 (s, 3H, Ac).5-Amino-2-[2 -hydroxy-1 -(2 -hydroxy-1 -hydroxymethyl-ethoxy)-ethyl]-1,2,4-triazin-3(2H)-one (9)was synthesized as a white solid by the procedure described in our paper [19]. Yield 92%, mp: 143-146 • C. UV (H 2 О): λ max 263.5 nm (lg ε 3.79).2-(α-L-arabinopyranosyl)-5-methylamino-1,2,4-triazin-3(2H)-one (11).…”