|Title:||Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers|
|Abstract:||A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (-)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner.|
|Inventor(s):||Liotta; Dennis C. (Stone Mountain, GA), Schinazi; Raymond F. (Decatur, GA), Choi; Woo-Baeg (North Brunswick, NJ)|
|Assignee:||Emory University (Atlanta, GA)|
|Filing Date:||Aug 20, 2003|
|Claims:||1. A method for the resolution of a mixture of the enantiomers of 2-hydroxylmethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (FTC), which has the structure ##STR00001## comprising the steps of: (i) providing the mixture of the enantiomers as an 5'-O-acylated derivative of the structure ##STR00002## wherein R is an acyl group; (ii) exposing the 5'-O-acylated derivative of 2-hydroxylmethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane to an enzyme selected from the group consisting of Amano PS-800 lipase and .alpha.-chymotrypsin under conditions that allow selective hydrolysis of the 5'-O-acyl group; and (iii) separating the 5'-O-hydrolyzed enantiomer from the 5'-O-unhydrolyzed enantiomer. |
2. The method according to claim 1, wherein the enzyme is Amano PS-800.
3. The method according to claim 1, wherein the enzyme is .alpha.-chymotrypsin.
4. The method of claim 1, wherein R is a residue of an alkyl carboxylic acid selected from the group consisting of acetic acid, propionic acid, butyric acid and pentanoic acid.
5. The method of claim 1, wherein R is a residue of a halo-substituted alkyl carboxylic acid selected from the group consisting of 2-chloropropionic acid, 2-chlorobutyric acid and 2-chloropentanoic acid.