Process for preparing tetrahydrobiopterin and analogs of tetrahydrobiopterin
View Patent ↗Process for the preparation of tetrahydrobiopterin from neopterin and/or 6-substituted pterins with an improved yield and a high stereoselectivity. Also disclosed herein are novel individual intermediates prepared in the preparation of tetrahydrobiopterin, such as selectively protected neopterin useful for the preparation of tetrahydrobiopterin.
1. A process for forming enantiomerically-enriched tetrahydrobiopterin (BH4) or a salt thereof from neopterin, comprising the steps of:
(a) protecting the primary amine group at C-2 of neopterin with an amino protecting group;
(b) converting the primary hydroxyl group of neopterin to a thioether; and
(c) reducing the thioether of step (b) to a methyl group.
2. The process of claim 1 , wherein step (c) also results in removal of the primary amine protecting group and erythro-selective reduction to form BH4 or a salt thereof.
3. The process of claim 1 , wherein the erythro-selective reduction comprises using Raney nickel and hydrogen.
4. The process of claim 1 , further comprising the step of removing the primary amine protecting group after step (c).
5. The process of claim 4 , wherein the removing comprises reacting with zinc dichloride in ethanol.
6. The process of claim 4 , further comprising the step of performing an erythro-selective reduction to form BH4 or a salt thereof.
7. The process of claim 6 , wherein the erythro-selective reduction comprises using (1) sodium borohydride in an alkaline medium or (2) hydrogen and a catalytic amount of platinum dioxide.