Development and optimization of the multi-gram synthesis of the antiviral 18-(Phthalimide-2-yl) ferruginol

Virus-induced diseases are very common in our society and continuously, we need new treatments for these challenging infections. We discovered by serendipity some years ago that the molecule 18-(Phthalimide-2-yl) ferruginol, an analogue of the natural diterpenoid (+)-ferruginol, a pharmacologically active molecule, was able to inhibit the spread of dengue virus type-2 (DENV-2) and human herpes virus 1 and 2 (HHV-1 and HHV-2). During the development and further studies of the above-mentioned analogue, we required scaling-up the synthesis of the target molecule. The synthesis was already reported by Waldvogel and co-workers in 2007 starting from the commercially available ca. 60% (+)-dehydroabietylamine in four synthetic steps. In this communication, we describe the several issues that we faced and propose an optimized experimental procedure in order to obtain this broad-spectrum antiviral, which we found that is even active against several strains of Zika virus.