Patent ID: 6897302
Filing Date: 2005-05-24
Classification: C07D,C07H

Abstract:
1. A method of synthesizing β-L-5-fluoro-2′,3′-dideoxy-2′,3′-didehydrocytidine (β-L-FD4C), the method comprising: (a) reacting L-xylose of formula I  with acetone in the presence of a first acid catalyst and a dehydrating agent to afford a diacetal of formula II (b) hydrolyzing the 2,3 acetal of the diacetal of formula II in the presence of a second acid catalyst to afford an acetal of formula III (c) acylating the alcohol moieties of the acetal of formula III in the presence of a base catalyst to afford a diester of formula IV (d) hydrolyzing the acetal moiety of the diester of formula IV in the presence of an acid to afford a diol of formula V (e) removing the hydroxyl groups of the diol of formula V to afford a glycal of formula VI (f) bis-protecting 5-fluorocytosine of formula VII  to afford bis-protected 5-fluorocytosine of formula VIII (g) coupling the glycal of formula VI with the bis-protected 5-fluorocytosine of formula VIII in the presence of a halogenating agent to afford a halogenated cytosine derivative of formula IX (h) treating the halogenated cytosine derivative of formula IX with metallic zinc and acetic acid to afford a dideoxy, didehydro cytidine derivative of formula X (i) hydrolyzing the ester moiety of the dideoxy, didehydro cytidine derivative of formula X in the presence of a base to afford β-L-5-fluoro-2′,3′-dideoxy-2′,3′-didehydrocytidine (β-L-FD4C) of formula XI