Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties

Abstract

Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

Solid‐Phase Microwave‐Assisted Ligand‐Free Suzuki‐Miyaura Cross‐Coupling of 5‐Iodouridine

“…The survey of reaction conditions showed that existing solution‐phase halouridine Suzuki‐Miyaura cross‐coupling reaction methods,–,,–,, are not suitable for use in solid‐phase synthesis of C‐5 uridine derivatives due to several limitations: i ) harsh reaction conditions ‐ reactions are carried out in the presence of strong alkaline solution (KOH) and currently available solid‐support linkage will not survive under coupling conditions; ii ) long reaction time (e. g. 24–48 h); iii ) elevated reaction temperature (∼200 °C); iv ) use of phosphine ligands, v ) poor yields and vi ) tedious purification processes . There is an urgent need to develop mild and practical reaction conditions for Suzuki‐Miyaura cross coupling of 5‐iodouridine with aryl/heteroaryl boronic acids, which can be transferable to solid‐phase organic synthesis.…”

Phenyl-imidazolo-cytidine Analogues: Structure–Photophysical Activity Relationship and Ability To Detect Single DNA Mismatch

“…Evaporation of the solvent gave the crude product, which was purified by column chromatography over silica gel, yielding 364 mg (55%) of a white solid. Mp: >218°C dec. 1 5-Nitro-2′-deoxyuridine-3′,5′-O-diacetate (15). 2′-Deoxyuridine, 14 (5 g, 0.02 mol), was treated with acetic anhydride (11 μL, 0.12 mol) in pyridine (200 mL) at room temperature overnight.…”

Efficient Synthesis of Unprotected C-5-Aryl/Heteroaryl-2'-deoxyuridine via a Suzuki-Miyaura Reaction in Aqueous Media

“…Therefore synthesis of unnatural nucleosides arises continuous interest because of their wide biological potential. For instance, 5-substituted 2'-deoxyuridines have been reported as efficient candidates in DNA labeling, modification, and other studies [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], and they also exhibit significant antiviral [ 18 , 19 , 20 , 21 , 22 , 23 ], antibacterial [ 24 ], and anticancer activities [ 25 , 26 , 27 ]. Due to the importance of modified nucleosides, all major classes of palladium-catalyzed reactions have been extensively developed to introduce various substituents [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

“…However protection/deprotection sequences induce generally a loss of material and increase the waste production. Recently, Suzuki-Miyaura reactions on unprotected 2'-deoxyuridines in an aqueous-organic solvent system were described, where tetrahydrofuran, acetonitrile, methanol or dimethylformamide was used as co-solvent [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 39 , 40 ]. To the best of our knowledge, only two examples in the 5-iodouridine [ 41 , 42 ] and one in the 2'-deoxy-uridine [ 43 ] series are reported in the literature where the experimental conditions required either tris(3-sulfonatophenyl)phosphine trisodium salt (TPPTS) as a specific ligand or palladium supported on reverse phase glass beads.…”