A Novel Synthesis of the Efficient Anti-Coccidial Drug Halofuginone Hydrobromide.

Background : Halofuginone hydrobromide ( 1 ) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. Methods : First, 7-bromo-6-chloroquinazolin-4(3 H )-one ( 2 ) was prepared from m -chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide ( 1 ) was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3 H )-one ( 4 ) by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS and ¹H-NMR. Besides, the protective effect of compound 1 -supplemented chicken diet at doses of 6, 3 and 1.5 mg per 1 kg were evaluated on chickens infected with E. tenella , by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology, respectively. Results : Halofuginone hydrobromide ( 1 ) was prepared successfully by and improved and innovative method based on traditional research. Moreover, the synthesized halofuginone hydrobromide significantly exhibited an anti-coccidial property. Conclusions : The fruitful work described in this Communication has resulted in halofuginone hydrobromide, which has a good pharmaceutical development prospects, becoming more available for large-scale production.