5-Bromo-2'-deoxycytidine

5-Bromo-2'-deoxycytidine Property

Boiling point:

510.8±60.0 °C(Predicted)

Density 

2.12±0.1 g/cm3(Predicted)

RTECS 

HA3705000

storage temp. 

Store at 0°C

solubility 

DMSO: Soluble
Water: Soluble

form 

Powder

pka

14.03±0.60(Predicted)

color 

White to Pale Yellow

CAS DataBase Reference

1022-79-3(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

40

Safety Statements 

22-36

HS Code 

29389090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

5-Bromo-2'-deoxycytidine Chemical Properties,Usage,Production

Uses

5-Bromo-2'-deoxycytidine (BrdC) is a brominated derivative of the deoxyribonucleoside 2’-deoxycytidine. It induces DNA cross-linking and the formation of DNA strand breaks when incorporated into a DNA fragment in place of cytosine and exposed to UVB damage. BrdC inhibits cytopathogenicity induced by herpes simplex virus 1 (HSV-1) and HSV-2 in infected primary rabbit kidney (PRK) cells (MICs = 0.2-0.3 μg/ml). It decreases the survival of U-1 melanoma cells and AG1522 non-cancerous cells and induces sensitization of both to radiation. BrdC also sensitizes tumors to radiation and reduces tumor volume in a mouse model of glioma using RT-2 cells infused with an adenovirus expressing HSV thymidine kinase (ADV-TK) after implantation. In vivo, BrdC is converted to 5-bromo-2'-deoxyuridine (BrdU) and has been used to label cardiac progenitor cells (CPCs) in a rat model of myocardial infarction.

Synthesis

The general procedure for the synthesis of 4-amino-5-bromo-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-ones, using 4-amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one as a starting material was carried out in the following manner: under stirring conditions, 2 '-O-methyluridine (5, 0.103 g, 0.4 mmol) was dissolved in aqueous acetonitrile (H2O:CH3CN = 1:9, 5 mL). NaN3 (0.104 g, 1.6 mmol) was then added and SMBI (0.101 g, 0.44 mmol) was added at room temperature. The reaction mixture was stirred continuously and the progress of the reaction was monitored by thin layer chromatography (TLC). The reaction was completed after about 1.5 h. The reaction mixture was filtered, concentrated under reduced pressure and co-evaporated with acetonitrile (2 x 2 mL) to remove residual water. The crude product was purified by column chromatography using a solvent mixture of dichloromethane (DCM) and methanol (MeOH) (4%-6% MeOH in DCM, v/v) as eluent, resulting in purified bromonucleoside 6 (0.117 g, 93% yield) as a white solid.

References

[1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 5, p. 1007 - 1013
[2] Synthesis, 2009, # 23, p. 3957 - 3962
[3] European Journal of Organic Chemistry, 2010, # 24, p. 4713 - 4718
[4] Molecules, 2013, vol. 18, # 10, p. 12740 - 12750
[5] Journal of the American Chemical Society, 1959, vol. 81, p. 1756
[6] THEODORE S. LAWRENCE M.D. PH.D.  Mary A D Ph D. Selective radiosensitization and cytotoxicity of human melanoma cells using halogenated deoxycytidines and tetrahydrouridine[J]. International Journal of Radiation Oncology Biology Physics, 1989, 16 5: Pages 1243-1246. DOI: 10.1016/0360-3016(89)90291-5
[7] MAGDALENA ZDROWOWICZ . 5-Bromo-2′-deoxycytidine—a potential DNA photosensitizer1[J]. Organic & Biomolecular Chemistry, 2016, 14 39: Pages 9312-9321. DOI: 10.1039/c6ob01446a
[8] E DE CLERCQ. Antiviral, antimetabolic, and cytotoxic activities of 5-substituted 2’-deoxycytidines.[J]. Molecular Pharmacology, 1982, 21 1: 217-223.
[9] DAVID BRUST. Radiosensitization of rat glioma with bromodeoxycytidine and adenovirus expressing herpes simplex virus-thymidine kinase delivered by slow, rate-controlled positive pressure infusion[J]. Cancer gene therapy, 2000, 7 5: 778-788. DOI: 10.1038/sj.cgt.7700168
[10] LEONARDO BOCCHI. Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.[J]. ACS Applied Bio Materials, 2011: e17750. DOI: 10.1371/journal.pone.0017750