Synthesis of (6S)-5-methyl-5,6,7,8-tetrahydrofolic acid
OwnerGerald Jones, Joseph Laurent +2inventors
InventorsGerald Jones, Joseph Laurent, Scott Goodrich, George Maguire
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Abstract
A process for the large-scale chemoenzymatic production of (6S)-5-methyl-5,6,7,8-tetrahydrofolic acid, also known as (6S)-5-methylTHFA, the process comprising the steps of: (1) reducing folic acid (FA) so as to yield dihydrofolic acid (DHFA); (2) stereoselectively reducing DHFA with dihydrofolate reductase (DHFR) in the presence of NADP/NADPH, glucose and GluDH so as to yield (6S)-THFA; (3) converting (6S)-THFA to (6S)-5-methylTHFA; and (4) isolating (6S)-5-methylTHFA.
Claims14
A process for the large-scale chemoenzymatic production of (6S)-5-methyl-5,6,7,8-tetrahydrofolic acid, also known as (6S)-5-methylTHFA, the process comprising the steps of:
- (1) reducing commercially available folic acid (FA) with zinc powder under basic conditions to yield dihydrofolic acid (DHFA);
- (2) stereoselectively reducing DHFA with dihydrofolate reductase (DHFR) in the presence of an NADP/NADPH recycling system, glucose and GluDH so as to yield (6S)-THFA;
- (3) converting (6S)-THFA to (6S)-5-methylTHFA in situ by conventional methods;
- and
- (4) isolating (6S)-5-methylTHFA as its calcium salt.
A chemoenzymatic process for producing calcium (6S)-5-methylTHFA, comprising the steps of:
- allowing DHFR to act upon DHFA in the presence of NADP, NADPH glucose and GluDH;
- accumulating (6S)-THFA in aqueous solution and converting it in situ to (6S)-5-methylTHFA;
- and
- recovering (6S)-5-methylTHFA as its calcium salt therefrom.
A process for the large-scale chemoenzymatic production of (6S)-5-methyl-5,6,7,8-tetrahydrofolic acid, also known as (6S)-5-methylTHFA, the process comprising the steps of:
- (1) reducing folic acid (FA) so as to yield dihydrofolic acid (DHFA);
- (2) stereoselectively reducing DHFA with dihydrofolate reductase (DHFR) in the presence of NADP/NADPH, glucose and GluDH so as to yield (6S)-THFA;
- (3) converting (6S)-THFA to (6S)-5-methylTHFA;
- and
- (4) isolating (6S)-5-methylTHFA.
Dependencies are inferred from the claim text.