The Synthesis Of Clevudine (L-FMAU)

As a common and frequently encountered disease, the infect of Hepatitis B Viruse(HBV) has great hazard to human's health, but the clinical therapeutical effects of anti-HBV drugs are not satisfying. Clevudine(L-FMAU) has potent anti-HBV activity which does not show any aparent toxicities. The anti-HBV activity of clevudine can sustain for 6 months after therapy. Besides, the combinaion of clevudine and other anti-HBV agents can increase therapeutical effect. Clevudine is currently considered as a clinical candidate for treatment of chronic HB V infection.Three methods of synthesis of clevudine were reported. We designed a relatively proper synthesis route based on references, and improved the synthesis technology. KHF2 and 48%HF was replaced by Et3N.3HF (a new style fluoric agent). The condition of reaction was greatly improved in fluorination. A trial was also taken on decreasing steps and increasing yields. The target compound clevudine was synthesized from L-ribose by 9 steps and the total yield was 5%.