Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1998-07-23
2003-01-28
Wilson, James O. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S028500, C536S028510, C536S028520, C536S028530, C536S028540, C536S028100, C536S025300, C536S025310
Reexamination Certificate
active
06512107
ABSTRACT:
The present invention relates to an improved process for preparing 2′-fluoro-5-methyl-&bgr;-L-arabinofuranosyluridine (generic name: Levovir, hereinafter referred to as “L-FMAU”) represented by formula (1), which shows anti-viral activity, especially potent anti-viral activity against hepatitis B-virus (HBV) and Epstein-Barr virus (EBV).
BACKGROUND OF THE INVENTION
International Publication No. WO 95/20595, and U.S. Pat. Nos. 5,587,362; 5,567,688; and 5,565,438 disclose L-FMAU and derivatives of formula (2):
in which R′ represents purine or pyrimidine base; and
R″ represents hydrogen, acyl, alkyl, monophosphate, diphosphate or triphosphate.
Nucleoside compounds of formula (2) exhibit anti-viral activity against HBV and EBV. Among these nucleoside compounds, L-FMAU shows particularly potent anti-viral activity against HBV and EBV with very low cytotoxicity and is, therefore, preferred as an anti-viral agent. Nucleoside compounds of formula (2), including L-FMAU, are useful in the prevention and treatment of HBV infections and related conditions, such as anti-HBV antibody positive and HBV-positive conditions, chronic liver inflammation caused by HBV, cirrhosis, acute hepatitis, fulminant hepatitis, chronic persistent hepatitis, and fatigue. In addition, they can also be used for the treatment of EBV-associated disorders.
According to the method disclosed in International Publication No. WO 95/20595, L-FMAU of formula (1) may be prepared using L-xylose of formula (3) as a starting material:
L-xylose of formula (3) cannot be obtained from natural substances and must therefore be produced by synthetic methods. When L-xylose is used as the starting material, the production cost of L-FMAU is therefore very high.
It has now been discovered that L-FMAU can be economically prepared from L-arabinose, which is present in many natural substances and, thus, is an inexpensive starting material, thereby completing the present invention.
SUMMARY OF THE INVENTION
An improved process for preparing L-FMAU is provided which uses L-arabinose as the starting material.
REFERENCES:
patent: 5565438 (1996-10-01), Chu et al.
patent: 5567688 (1996-10-01), Chu et al.
patent: 5587362 (1996-12-01), Chu et al.
patent: 5808040 (1998-09-01), Chu et al.
patent: WO 89/07602 (1989-08-01), None
patent: WO 95/20595 (1995-08-01), None
John Wiley,Protective Groups in Organic Synthesis,second edition, 1991.
Vojtech Bilik, L-Ribose by catalyzed Epimerization of L-Arabinose, Chemical Abstracts, 81:78189.
Choi Yongseok
Chu Chung K.
Du Jinfa
King & Spalding
Knowles, Esq. Sherry M.
Owens, Jr. Howard V.
The University of Georgia Research Foundation
Wilson James O.
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