5-Iodouracil is a halogenated pyrimidine that can be used in nucleoprotein photo-crosslinking via RNA substitution. 5-Iodouracil is used in thymidine phosphorylase targeted imaging and therapy. Studies show that DNA N-glycosylase MED1 exhibited higher preference for 5-Iodouracil and halogenated bases over non-halogenated ones.
The general procedure for the synthesis of 5-iodouracil (5-IUra) from pyrimidine-2,4(1H,3H)-dione (Ura) is as follows:
Example 1 Synthesis of 5-halogenated uracil (5-X-Ura)
Preparation of 5-iodouracil (5-IUra) and 5-bromouracil (5-BrUra) from Ura:
1. Prepare a solution of 1,3,4,6-tetrachloro-3a,6a-diphenylglycuronium in chloroform (concentration 0.5 mg/mL). All reagents were available from Sigma Chemical Co. (St. Louis, MO) unless otherwise noted.
2. Dry 0.5 mL (containing 250 μg, 578 μmol) of the above solution using a stream of nitrogen.
3. 300 μL of Ura (2610 μmol, 8.7 M, dissolved in 0.25 M potassium phosphate buffer, pH 7.5) was added.
4. 100 μL NaI or NaBr (670 μmol, 6.7 M aqueous solution) was subsequently added to the reaction system.
5. The reaction mixture was heated at 60 °C for 15 min.
6. Upon completion of the reaction, the yield was 79% for 5-IUra and 56% for 5-BrUra, depending on the halide used.
7. At the end of the reaction, the reaction mixture was diluted with water and the products were analyzed by reversed-phase high performance liquid chromatography (HPLC).
8. HPLC mobile phase conditions: 20-50 mM acetic acid and 6-16% acetonitrile (ACN).
Note: This method is suitable for the synthesis of materials on a small scale and also for the therapeutic isotope labeling of Ura by replacing non-radioactive halides with radioisotopes such as [82Br] or [125I].
[1] Tetrahedron Letters, 2002, vol. 43, # 8, p. 1381 - 1386
[2] Synlett, 2005, # 8, p. 1263 - 1266
[3] Helvetica Chimica Acta, 2015, vol. 98, # 7, p. 953 - 960
[4] Synthesis, 2004, # 11, p. 1869 - 1873
[5] Synthesis, 1995, # 8, p. 926 - 928
