201996-55-6Relevant articles and documents
Enzymatic synthesis of ribo- and 2′-deoxyribonucleosides from glycofuranosyl phosphates: An approach to facilitate isotopic labeling
Zhang, Wenhui,Turney, Toby,Surjancev, Ivana,Serianni, Anthony S.
, p. 125 - 133 (2017/08/08)
Milligram quantities of α-D-ribofuranosyl 1-phosphate (sodium salt) (αR1P) were prepared by the phosphorolysis of inosine, catalyzed by purine nucleoside phosphorylase (PNPase). The αR1P was isolated by chromatography in >95% purity and characterized by 1H and 13C NMR spectroscopy. Aqueous solutions of αR1P were stable at pH 6.4 and 4 °C for several months. The isolated αR1P was N-glycosylated with different nitrogen bases (adenine, guanine and uracil) using PNPase or uridine phosphorylase (UPase) to give the corresponding ribonucleosides in high yield based on the glycosyl phosphate. This methodology is attractive for the preparation of stable isotopically labeled ribo- and 2′-deoxyribonucleosides because of the ease of product purification and convenient use and recycling of nitrogen bases. The approach eliminates the need for separate reactions to prepare individual furanose-labeled ribonucleosides, since only one ribonucleoside (inosine) needs to be labeled, if desired, in the furanose ring, the latter achieved by a high-yield chemical N-glycosylation. 2′-Deoxyribonucleosides were prepared from 2′-deoxyinosine using the same methodology with minor modifications.
Chemical synthesis of 13C labeled anti-HIV nucleosides as mass-internal standards
Saito, Yoshio,Zevaco, Thomas A,Agrofoglio, Luigi A
, p. 9593 - 9603 (2007/10/03)
Synthesis of [13C5]-labeled anti-HIV nucleosides, e.g. d4T, ddI, ddA, is described. The methodology used has been optimized due to the very high cost of the starting compound. The key step of this approach was the stereoselective dehomologation of 1,2:5,6-di-O-isopropylidene-3-oxo-α-D-glucofuranose (2) with periodic acid and sodium borohydride, which gave optically pure ribose derivative as the exclusive product. Nucleoside derivatives 6a-c were obtained from ribosylation of 5 with persilylated nucleobases under Vorbru?ggen conditions. Deoxygenation of 9a-c under Corey-Winter conditions afforded the desired labeled nucleoside analogues 12a-c.
13C-enriched ribonucleosides: Synthesis and application of 13C-1H and 13C-13C spin-coupling constants to assess furanose and N-glycoside bond conformations
Kline, Paul C.,Serianni, Anthony S.
, p. 7373 - 7381 (2007/10/02)
Adenosine (1), cytidine (2), guanosine (3), and uridine (4) have been prepared chemically with 13C enrichment (99 atom %) at C1′ and C2′ of the ribose ring. Reliable synthetic protocols have been developed to permit access to millimole quantities of labeled ribonucleosides required for structural studies of stable isotopically labeled oligonucleotides and for in vivo metabolism studies. High-resolution 1H and 13C NMR spectra of the enriched ribonucleosides have been obtained, and 13C-13C and 13C-1H spin-coupling constants have been measured for pathways within the β-D-ribofuranose ring and across the N-glycoside bond. Related couplings were determined in methyl α- and β-D-ribofuranosides (5, 6), and in two conformationally constrained nucleosides, 2,2′-anhydro-(1-β-D-arabinofuranosyl)uracil (7) and 2′,3′-O-isopropylidene-2,5′-O-cyclouridine (8). The latter data were used to construct a crude Karplus curve for the 13C-C-N-13C coupling pathway across the N-glycoside bond in 1-4. 1H-1H, 13C-1H, and 13C-13C coupling data are used to evaluate current models describing the conformational dynamics of 1-4 in aqueous solution.
