Synthesis of the Antimalarial Compound FR900098
Malaria continues to be a potentially fatal threat to almost half of the world's population, mainly in third world countries in Africa and South America. Resistance against the most common and affordable antimalarial drugs is a widespread problem. FR900098 represents an improved derivative of the new anti-malarial drug fosmidomycin, and acts through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, which is an essential enzyme of the mevalonate-independent pathway of isoprenoid biosynthesis. It has been shown to inhibit the growth of multidrug-resistant strains of Plasmodium falciparum in vitro. Furthermore, FR900098 has been demonstrated to cure mice infected with the rodent malaria parasite Plasmodium vinckei. FR900098 has very low toxicity in animals and humans, and demonstrates excellent antibacterial activity against most gram-negative bacteria. However, it has not achieved widespread clinical use. Therefore, FR900098 is a candidate for further development. We show here a synthetic route to make the intermediates that would lead to the total synthesis of FR900098. We were able to obtain an intermediate that was three steps away from the total synthesis of FR900098. The final three steps of the route are well known reactions that should allow for the total synthesis of FR900098.