Uses
O6-Benzylguanine is an effective substrate and efficient inactivator of DNA alkyltransferase. O6-Benzylguanine is an inhibitor of MGMT. It is also used as an important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals and dyestuff.
Biochem/physiol Actions
O6-Benzylguanine (O6BG) inhibits methylguanine methyltransferase (MGMT) by blocking the active site through benzyl group transfer. The use of O6BG with bis-chloroethylnitrosourea (BCNU) or carmustine is effective in treating solid tumors including lymphomas, melanomas and sarcoma.
Synthesis
GENERAL STEPS: Benzyl alcohol (37.5 g, 0.347 mol) was mixed with sodium hydroxide (2.96 g, 0.074 mol) and heated until the sodium hydroxide was completely dissolved. After the reaction mixture was cooled, 2-amino-6-chloropurine (6.00 g, 0.035 mol) was added and the reaction was stirred at 80-90 °C for 5 hours. After completion of the reaction, methyl tert-butyl ether (120 mL) was added to the reaction mixture and extracted twice with sodium hydroxide solution (70 mL). The alkaline aqueous layers were combined, washed with toluene and subsequently evaporated to remove the toluene. The solution was neutralized to pH 6-8 with 35% hydrochloric acid and the precipitated crystals were collected by filtration. The resulting crude product 2-amino-6-(benzyloxy)purine (7.60 g, 0.032 mol, 92% yield) was dried under reduced pressure.
References
[1] Patent: WO2003/84957, 2003, A1. Location in patent: Page/Page column 9-10
[2] Nucleosides and Nucleotides, 1999, vol. 18, # 10, p. 2219 - 2231
[3] Helvetica Chimica Acta, 2012, vol. 95, # 12, p. 2621 - 2634
[4] Tetrahedron, 2007, vol. 63, # 24, p. 5323 - 5327
[5] Synthetic Communications, 2003, vol. 33, # 6, p. 941 - 952
