Novel and efficient syntheses of 3′,5′-diamino derivatives of 2′,3′,5′-trideoxycytidine and 2′,3′,5′-trideoxyadenosine. Protonation behavior of 3′,5′-diaminonucleosides

Abstract

Abstract-High yielding synthetic routes to 3',5'-diamino-2',3',5'-trideoxycytidine and 3',5'-diamino-2',3',5'-trideoxyadenosine are described. In addition, the protonation behavior of 3',5'-diamino-2',3',5'-trideoxycytidine, 3',5'-diamino-2',3',5'-trideoxyadenosine, 3',5'-diamino-3',5'-dideoxythymidine, and 3',5'-diamino-2',3',5'-trideoxyuridine has been studied by means of pH-metric measurements and NMR spectroscopy. The ionization constants and the sequence of protonation sites have been determined.

Design, Synthesis, and Biological Evaluation of 1-[(2-Benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with an Improved Drug Resistance Profile

“…Compounds 4a – 5b were silylated in situ with N , O -bis(trimethylsilyl)acetamide (BSA) and then N-1 alkylated with the appropriate alkyl chloromethyl ether, in the presence of LiI, to give 6a – 9b , in good yield, followed by reaction with aqueous dimethylamino solution to get 10a – 11b . , Finally, the uracil moiety was successfully converted to the 4-(1,2,4-triazolyl)pyrimidinone derivatives. Without purification, subsequent ammonia treatment yielded the target compounds 12a – 15b . − Structure assignments of these compounds were identified by NMR and mass spectral data.…”

Synthesis of 2′-O-Methyl/2′-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies

“…Instrumentation. NMR spectra ( 1 H, 13 C, 19 F, and 31 P) were measured on a Varian Mercury-400 ( 1 H 400.13 MHz, 13 C 100.6 MHz, 19 F 376.5 MHz, and 31 P 162.0 MHz) spectrometer or on a Bruker DPX-300 ( 1 H 300.13 MHz, 13 C 75.5 MHz, and 31 P 121.5 MHz). Chemical shifts for 1 H, 13 C, 19 F, and 31 P NMR are given in parts per million (ppm) from the residual solvent signal.…”

“…The use of 2-methoxyethanol instead of methanol during above procedure failed to generate 2′-O-MOE derivative 13. The synthesis of compound 13 was carried out by adding the anhydrouridine 11 to a mixture of 2-methoxyethanol and aluminum, previously heated under reflux for 2 h, according to the conditions described by Legorburu et al 19 After 48 h under reflux, 2′-O-MOE-L-uridine (13) was isolated in 55% yield.…”

Biocatalysis Applied to the Synthesis of Nucleoside Analogs

“…Some routes for the synthesis of new analogs of this kind of compounds have been described [26] .A modifi ed route for the preparation of 3 ′ ,5 ′ -diamino -3 ″ ,5 ′ -trideoxythymidine is outlined in Scheme 10.10 . The reaction, which takes place in four steps with an overall yield of 63%, is an improvement on the earlier described process [27] .…”