Method for producing L-biopterin
View Patent ↗To provide a method for producing L-biopterin on a large industrial scale by using a reagent which is inexpensive and easy to handle, without requiring a use of any particular equipment or plants. A method for porducing a biopterin derivative represented by the formula (6): wherein R 1 and R 2 , which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group, comprising: reacting a compound belonging to triacetoxy-5-deoxy-L-arabinose phenylhydrazones represented by the formula (4): wherein R 1 and R 2 are the same as defined above, with 6-hydroxy-2,4,5-triaminopyrimidine (5) under catalytic influence of a Lewis acid in an aqueous solvent.
1. A method for producing a compound represented by formula (6):
wherein R 1 and R 2 , which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group, comprising:
reacting a triacetoxy-5-deoxy-L-arabinose phenylhydrazone of formula (4):
wherein R 1 and R 2 which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group;
with 6-hydroxy-2,4,5-triaminopyrimidine (5) under catalytic influence of a Lewis acid in an aqueous solvent.
2. The method according to claim 1 , wherein said aqueous solvent is water or a water-lower alcohol mixed solvent.
3. The method according to claim 1 , wherein said Lewis acid is an aqueous Lewis acid catalyst.
4. The method according to claim 1 , wherein said Lewis acid is one selected from the group consisting of alkali metal perchlorates, alkali metal sulfonates, alkali metal sulfates and alkali metal halides.
5. A method for producing 1′,2′-O-diacetyl-L-biopterin, comprising oxidizing the compound represented by formula (6) obtainable by a method according to claim 1 .
6. The method according to claim 5 , wherein said oxidizing step is carried out using hydrogen peroxide.
7. A method for producing L-biopterin, comprising hydrolyzing the 1′,2′-O-diacetyl-L-biopterin obtainable by a method according to claim 5 .
8. The method according to claim 7 , wherein said hydrolyzing step is carried out in the presence of hydrochloric acid.
9. The method according to claim 1 , wherein said compound represented by formula (4) is obtained by:
reacting a compound represented by the formula (3) with an acetylating agent in the presence of a catalytic quantity of dialkylaminopyridine; wherein formula (3) is:
wherein R 1 and R 2 , which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group.
10. The method according to claim 9 , wherein said acetylating agent is one selected from the group consisting of acetic anhydride and acetyl halides.
11. The method according to claim 9 , wherein said compound represented by formula (3) is obtained by:
reacting 5-deoxy-L-arabinose with a hydrazine compound represented by formula (2) under acidic conditions in water or in a water-organic two-layer solvent;
wherein the compound of formula 2 is:
wherein R 1 and R 2 , which are the same or different from each other, each represents an hydrogen atom, an alkyl group, or an aryl group.
12. The method according to claim 11 , wherein said organic solvent is one selected from the group consisting of alkyl acetates, lower alkyl halides, aromatic hydrocarbons and ethers.
13. The method of claim 5 , wherein the oxidizing step is carried out without using iodine.
14. The method of claim 7 which produces at least 14 kg of biopterin per 1,000 liters of reaction equipment capacity.