50-90-8

Usage

Uses

Used in Pharmaceutical Compositions:
5-Chloro-2'-deoxyuridine is used as a thymidine analog in pharmaceutical compositions, where it can be utilized for various therapeutic purposes due to its ability to alter DNA processing and replication.
Used in Antiviral Applications:
CldU is used as an antiviral compound due to its ability to interfere with the replication of viral DNA, making it a potential candidate for the development of new antiviral drugs.
Used in DNA Damage and Repair Studies:
5-Chloro-2'-deoxyuridine is used as a thymidine analog to study the miscoding potential of hypochlorous acid damage to DNA and DNA precursors. This helps researchers understand the mechanisms of DNA damage and repair, which can be crucial for developing new strategies to combat various diseases.
Used in DNA Replication Research:
When used with antibody-based immunofluorescent imaging, CldU incorporation may be used in protocols to identify sites of DNA replication. This allows researchers to study the process of DNA replication and its regulation, which is essential for understanding cell division and the development of cancer.
Used in Combination with Other Thymidine Analogs:
CldU may be used as a labeling substrate in conjunction with other halogenated uridine labeling substrates such as iododeoxyuridine (IdU). This enables researchers to label and track different populations of cells or tissues over time, providing valuable insights into cellular processes and dynamics.
Used in Diagnostic and Research Applications:
CldU's ability to be detected immunologically in cells and tissues makes it a useful tool for diagnostic and research applications, where it can be employed to study various aspects of cellular biology, including cell proliferation, DNA repair, and mutagenesis.

Biochem/physiol Actions

DNA labeled with 5-chloro-2′-deoxyuridine (CldU) serves as an effective tool to analyze and quantify DNA replication, repair, and recombination. CldU is a potent mutagen, clastogen, and toxicant. It is used as a thymidine analog and is found to alter the dNTP pools and might lead to cell-cycle arrest. CldU produces sister-chromatid exchange but has less response to ionizing radiation compared to other thymine analogs. 5-Chloro-2′-deoxyuridine (CldU) is used to study the miscoding potential of hypochlorous acid damage to DNA and DNA precursors. When used with antibody based immunofluorescent imaging, 5-Chloro-2′-deoxyuridine incorporation may be used in protocols to identify sites of DNA replication. CldU may be used as a labeling substrate in conjunction with other halogenated uridine labeling substrates such as iododeoxyuridine (IdU).

Upstream product

• 951-78-0 2'-deoxyuridine 
• 6046-63-5 1-(3,5-di-O-acetyl-β-D-2-deoxyribofuranosyl)-5-chlorouracil 
• 54-42-2 5-Iodo-2'-deoxyuridine 
• 1820-81-1 5-chlorouracil 
• 50-89-5 thymidine 
• 13030-62-1 3',5'-di-O-acetyl-2'-deoxyuridine 

Downstream Products

• 1820-81-1 5-chlorouracil 
• 255723-76-3 5-chloro-2’-deoxy-5’-O-dimethoxytrityluridine 
• 6046-63-5 1-(3,5-di-O-acetyl-β-D-2-deoxyribofuranosyl)-5-chlorouracil 
• 140226-27-3 4'-azido-5-chloro-2',5'-dideoxy-5'-iodo-3'-O-(4-methoxybenzoyl)uridine 
• 139418-97-6 4'-azido-5-chloro-2'-deoxyuridine 
• 58349-26-1 5-Chloro-5'-O-p-tolylsulphonyl-2'-deoxyuridine 

Relevant academic research and scientific papers

Thermally reversible and irreversible interstrand photocrosslinking of 5-chloro-2′-deoxy-4-Thiouridine modified DNA oligonucleotides

We describe highly efficient interstrand photocrosslinking of a DNA duplex containing 5-chloro-2′-deoxy-4-Thiouridine (ClSdU) in one strand, proceeding via a two-step photochemical cascade, involving the formation of a thermally reversible crosslink between ClSdU and thymidine in the target strand and its subsequent conversion to a thermally stable fluorescent crosslink. These results show that ClSdU has great potential to be a valuable DNA photo-crosslinking reagent for chemical biology applications.

Bio-catalytic synthesis of unnatural nucleosides possessing a large functional group such as a fluorescent molecule by purine nucleoside phosphorylase

Unnatural nucleosides are attracting interest as potential diagnostic tools, medicines, and functional molecules. However, it is difficult to couple unnatural nucleobases to the 1′-position of ribose in high yield and with β-regioselectivity. Purine nucleoside phosphorylase (PNP, EC2.4.2.1) is a metabolic enzyme that catalyses the conversion of inosine to ribose-1α-phosphate and free hypoxanthine in phosphate buffer with 100% α-selectivity. We explored whether PNP can be used to synthesize unnatural nucleosides. PNP catalysed the reaction of thymidine as a ribose donor with purine to produce 2′-deoxynebularine (3, β form) in high conversion (80%). It also catalysed the phosphorolysis of thymidine and introduced a pyrimidine base with a halogen atom substituted at the 5-position into the 1′-position of ribose in moderate yield (52-73%), suggesting that it exhibits loose selectivity. For a bulky purine substrate [e.g., 6-(N,N-di-propylamino)], the yield was lower, but addition of a polar solvent such as dimethyl sulfoxide (DMSO) increased the yield to 74%. PNP also catalysed the reaction between thymidine and uracil possessing a large functional fluorescent group, 5-(coumarin-7-oxyhex-5-yn) uracil (C4U). Conversion to 2′-deoxy-[5-(coumarin-7-oxyhex-5-yn)] uridine (dRC4U) was drastically enhanced by DMSO addition. Docking simulations between dRC4U and E. coli PNP (PDB 3UT6) showed the uracil moiety in the active-site pocket of PNP with the fluorescent moiety at the entrance of the pocket. Thus, the bulky fluorescent moiety has little influence on the coupling reaction. In summary, we have developed an efficient method for producing unnatural nucleosides, including purine derivatives and modified uracil, using PNP.

Biotransformation of halogenated nucleosides by immobilized Lactobacillus animalis 2′-N-deoxyribosyltransferase

An immobilized biocatalyst with 2′-N-deoxyribosyltransferase (NDT) activity, Lactobacillus animalis NDT (LaNDT), was developed from cell free extracts. LaNDT was purified, characterized and then immobilized by ionic interaction. Different process parameters were optimized, resulting in an active derivative (2.6 U/g) able to obtain 1.75 mg/g of 5-fluorouracil-2′-deoxyriboside, an antimetabolite known as floxuridine, used in gastrointestinal cancer treatment. Furthermore, immobilized LaNDT was satisfactorily used to obtain at short reaction times other halogenated pyrimidine and purine 2′-deoxynucleosides such as 6-chloropurine-2′-deoxyriboside (4.9 U/g), 6-bromopurine-2′-deoxyriboside (4.3 U/g), 6-chloro-2-fluoropurine-2′-deoxyriboside (5.4 U/g), 5-bromo-2′-deoxyuridine (2.8 U/g) and 5-chloro-2′-deoxyuridine (1.8 U/g) compounds of pharmaceutical interest in antiviral or antitumor treatments. Besides, increasing the biocatalyst amount 8 times per volume unit allowed obtaining a 5-fold improvement in floxuridine biotransformation. The developed biocatalyst proved to be effective for the biosynthesis of a wide spectrum of nucleoside analogues by employing an economical, simple and environmentally friendly methodology.

Synthesis and properties of DNA containing cyclonucleosides

Here, we present efficient syntheses of the R and S diastereomers of 8,5′-cyclo-2′-deoxyadenosine and 6,5′-cyclo-2′- deoxyuridine. We incorporated these interesting nucleosides into DNA to study how the cyclo linkage affects the stability of duplex formation.

Ionic liquid mediated synthesis of 5-halouracil nucleosides: Key precursors for potential antiviral drugs

Synthesis of antiviral 5-halouracil nucleosides, also used as key precursors for the synthesis of other potential antiviral drugs, has been demonstrated using ionic liquids as convenient and efficient reaction medium.

Highly efficient method for C-5 halogenation of pyrimidine-based nucleosides in ionic liquids

A novel, highly efficient, convenient, and benign methodology for C-5 halogenation of pyrimidine-based nucleosides has been developed using N-halosuccinimides as halogenating reagents without using any catalyst in ionic liquid medium. The ionic liquids were successfully recovered and reused for all the reactions. Georg Thieme Verlag Stuttgart.

Importance of 3′-hydroxyl group of the nucleosides for the reactivity of thymidine phosphorylase from Escherichia coli

Thymidine phosphorylase in phosphate buffer catalyzed the conversion of thymidine to unnatural nucleosides. The 3′-OH, but not the 5′-OH of ribosyl moiety is necessary to be recognized as a substrate. Thus 3′-deoxythymidine could not convert to 5-fluorouracil-2′,3′- dideoxyribose. However, 5′-deoxythymidine was converted to 5-fluorouracil-2′,5′-dideoxyribose. Copyright

Photochemical halogen-exchange reaction of 5-iodouracil-containing oligonucleotides

Photoreactions of 5-iododeoxyuridine (d(I)U) and d(I)U-containing oligonucleotides in aqueous solutions in the presence of various inorganic salts have been investigated. In the presence of NaCl and NaBr, d(I)U and d(I)U-containing oligonucleotides undergo an efficient photochemical halogen-exchange reaction to give d(Cl)U and d(Br)U, respectively.

Antiviral agents

Nucleoside compounds of the formula STR1 wherein: B is a purine or a pyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH3 or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is STR2 where n is zero, one, two or three; and Z' is N3 or OCH3 ; provided that when X' and Y' are OH and Z' is N3, B is not cytosine, and when X' and Y' are OH and Z' is OCH3, B is not uracil, adenine or cytosine; and the pharmaceutically acceptable esters, ethers and salts thereof, have been found to have potent antiviral activity with a high therapeutic ratio.

A mild and efficient methodology for the synthesis of 5-halogeno uracil nucleosides that occurs via a 5-halogeno-6-azido-5,6-dihydro intermediate

A mild and efficient methodology for the synthesis of 5-halogeno (iodo, bromo, or chloro) uracil nucleosides has been developed. 5-Halo-2'-deoxyuridines 4a-c (84-95%), 5-halouridines 7a-c (45-95%), and 5-haloarabinouridines 8a-c (65-95%) were synthesized in good to excellent yields by the reaction of 2'-deoxyuridine (2), uridine (5) and arabinouridine (6), respectively with iodine monochloride, or N-bromo (or chloro)succinimide, and sodium azide at 25-45°C. These C-5 halogenation reactions proceed via a 5-halo-6-azido-5,6-dihydro intermediate (3), from which HN3 is eliminated, to yield the 5-halogeno uracil nucleoside. The 5-halo-6-azido-5,6-dihydro intermediate products (10a, 10b) could be isolated from the reaction of 3',5'-di-O-acetyl-2'-deoxyuridine (9) with iodine monochloride or N-bromosuccinimide and sodium azide at 0°C. The isolation of 10a, 10b indicates that the C-5 halogenation reaction proceeds via a 5-halo-6-azido-5,6-dihydro intermediate.