Synthesis and chemical carcinogen inhibitory activity of 2-tert-butyl-4-hydroxyanisole.
The title compound 1 was selectively synthesized in its pure isomeric form by means of the hydroxyl-protecting reagent dimethyl-tert-butylchlorosilane. Exclusive silylation occurred at the less hindered hydroxyl group of 3. Dimethyl sulfate methylation of 4 gave 5 in excellent yield. Compound 1 was then obtained by acid hydrolysis of 5. The two BHA isomers, 1 and 2, were tested on their inhibitory effects toward benzo[alpha]pyrene-induced neoplasia in the forestomach of the ICR/Ha mouse. Both isomers, when added to the diet, reduced the number of mice with tumors and the number of tumors per mouse. Isomer 1, which has the less hindered free hydroxyl group, showed higher inhibitory effect in the present experimental model.
D000818:Animals; D000840:Anisoles / Q000138:chemical synthesis*; D001580:Benzopyrenes / Q000037:antagonists & inhibitors / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D005260:Female; D007536:Isomerism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control
D000840:Anisoles; D001580:Benzopyrenes; D002273:Carcinogens; D002083:Butylated Hydroxyanisole