Reaction of 5-chlorouracil derivatives with cysteine

Journal Article · Wed Aug 02 04:00:00 EDT 1978 · J. Am. Chem. Soc.; (United States)

DOI:https://doi.org/10.1021/ja00484a044· OSTI ID:6543759

Pal, B C

5-Bromo-2'-deoxyuridine reacts with cysteine to produce 2'-deoxyuridine and 5-(cystein-S-yl)-2'-deoxyuridine in 2 : 1 and 1 : 2 molar ratio at pHs 7 and 12, respectively. 5-Chloro-2'-deoxyuridine as well as its 1-methyl analogue, on the other hand, does not react appreciably with cysteine at pH 7 but at pH 12 forms 5-(cystein-S-yl)-2'-deoxyuridine and its 1-methyl analogue, respectively, in better than 99 percent yield. A reaction mechanism is proposed to account for the role of halogen in influencing the course of this reaction. The first step is the addition of cysteine across the 5,6 double bond of the pyrimidine ring. In case of a good leaving group such as Br, attack of the cysteinyl anion on the 6 position leads to the formation of cysteine, 2'-deoxyuridine, and bromide. Parallel to this reaction, the 5 halogen (either Cl or Br) may undergo nucleophilic substitution by cysteine and form 5-(cystein-S-yl)-2'-deoxyuridine after base-catalyzed elimination of cysteine at the 6 position. Synthesis and ultraviolet absorption data of 1-methyl-5-chlorouracil, 1-methyl-5-(cysteine-S-yl)uracil, and 5-(cystein-S-yl)-2'deoxyuridine are reported.

• Research Organization: Oak Ridge National Lab., TN
• OSTI ID: 6543759
• Journal Information: J. Am. Chem. Soc.; (United States), Journal Name: J. Am. Chem. Soc.; (United States) Vol. 100:16; ISSN JACSA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AZINES
CARBOXYLIC ACIDS
CHEMICAL REACTION KINETICS
CHEMICAL REACTION YIELD
CHEMICAL REACTIONS
CYSTEINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
KINETICS
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PH VALUE
PYRIMIDINES
REACTION KINETICS
SPECTRA
SYNTHESIS
THIOLS
ULTRAVIOLET SPECTRA
URACILS
YIELDS