A practical synthesis of Funguard (FK463)

Abstract

Fujisawa Pharmaceutical Co. launched Funguard, a novel antifungal agent on December 6, 2002. The clinical studies of Funguard have shown its significant activity for the treatment of systemic Candidiasis and Aspergillosis without safety concerns. The original synthesis of Funguard involved expensive reagents, environmentally unfriendly metals and low yield. We investigated practical synthesis of Funguard amenable to a large scale synthesis to eliminate these problems. New synthetic methods established by these studies use a regioselective conversion of FR179342 to isoxazole following recrystallization to obtain FR203042. In addition, the isolated isomer is recovered as FR179342 after hydrolysis. The reported methods are advantageous over the original methods from the viewpoints of large scale manufactureability, and thus applied to industrial scale synthesis of Funguard.