Method for preparing isofagomine and its derivatives
View Patent ↗A method for preparing isofagomine, its derivatives, intermediates and salts thereof using novel processes to make isofagomine from D-(−)-arabinose and L-(−)-xylose.
1. A method for preparing isofagomine tartrate, comprising protecting the anomeric hydroxyl group of D-(−)-arabinose with a protecting group to form a glycoside; protecting the 2- and 3-hydroxyl groups of said glycoside using a 1,2-dione to form a triprotected arabinose derivative; converting said arabinose derivative to a triprotected xylose derivative; converting said xylose derivative to a triprotected nitrile; converting said nitrile to a protected diol and deprotecting said diol to form isofagomine in the presence of tartaric acid.
2. The method of claim 1 further comprising converting said arabinose derivative to said xylose derivative through an activated system wherein said activated system is optionally isolated before conversion.
3. The method of claim 1 further comprising converting said xylose derivative to said nitrile using an activated system, wherein said activated system is optionally isolated before conversion followed by displacement by a cyano source.
4. The method of claim 1 further comprising obtaining said nitrile after purifying said xylose derivative.
5. The method of claim 1 further comprising converting said arabinose derivative to said xylose derivative by a Mitsunobu inversion reaction to form an inverted ester derivative and saponification.
6. A method for preparing isofagomine tartrate, comprising protecting the anomeric hydroxyl group of D-(−)-arabinose with a protecting group to form a glycoside; protecting the 2- and 3-hydroxyl groups of said glycoside using a 1,2-dione to form a triprotected arabinose derivative; converting said arabinose derivative to a triprotected xylose derivative; converting said xylose derivative to a triprotected nitrile; converting said nitrile in the presence of tartaric acid to a protected isofagomine tartrate salt and deprotecting said isofagomine tartrate salt.
7. A method for preparing isofagomine tartrate, comprising protecting the anomeric hydroxyl group of D-(−)-arabinose with a protecting group to form a glycoside; protecting the 2- and 3-hydroxyl groups of said glycoside using a 1,2-dione to form a triprotected arabinose derivative; converting said arabinose derivative to a triprotected xylose derivative; converting said xylose derivative to a triprotected nitrile; reducing said nitrile to a triprotected primary amine; deprotecting said primary amine to a diol; and subjecting the diol to catalytic hydrogenation in the presence of tartaric acid.
8. The method of claim 1 wherein protecting of said anomeric hydroxyl group of D-(−)-arabinose is accomplished using an alcohol, an activating agent and optionally a solvent; and formation of said arabinose derivative is accomplished using an acid and an alcohol.
9. The method of claim 6 wherein protecting of said anomeric hydroxyl group of D-(−)-arabinose is accomplished using an alcohol, an activating agent and optionally a solvent; and formation of said arabinose derivative is accomplished using an acid and an alcohol.
10. The method of claim 7 wherein protecting of said anomeric hydroxyl group of D-(−)-arabinose is accomplished using an alcohol, an activating agent and optionally a solvent; and formation of said arabinose derivative is accomplished using an acid and an alcohol.