Processes for producing optically active 1-substituted 2-methylpyrrolidine
View Patent ↗The present invention relates to a process for producing an optically active 1,4-pentanediol by asymmetrically reducing 5-hydroxy-2-pentanone, which is easily available at low cost. The present invention also relates to a process for producing an optically active 1-substituted 2-methylpyrrolidine including sulfonylating the optically active 1,4-pentanediol to convert it to an optically active sulfonate compound, and reacting the compound with an amine. According to the processes of the present invention, an optically active 1,4-pentanediol and an optically active 1-substituted 2-methylpyrrolidine, which are useful as an intermediate for medicines and an intermediate for agricultural chemicals, can be simply produced from an inexpensive starting material.
1. A process for producing an optically active 1,4-pentanediol represented by formula (2):
(wherein * represents an asymmetric carbon atom) comprising asymmetrically reducing 5-hydroxy-2-pentanone represented by formula (1):
wherein said asymmetric reduction of 5-hydroxy-2-pentanone represented by formula (1) is catalyzed by an enzyme comprising the amino acid sequence of the reducing enzyme encoded by a vector selected from the group consisting of: pNTS1G of Escherichia coli HB101 (pNTS1G) (FERM BP-5835); pNTFPG of Escherichia coli HB101 (pNTFPG) (FERM BP-7117); pNTDRG1 of Escherichia coli HB101 (pNTDRG1) (FERM BP-08458); pNTRS of Escherichia coli HB101 (pNTRS) (FERM BP-08545); or pNTRGG1 of Escherichia coli HB101 (pNTRGG1) (FERM BP-7858).
2. The process according to claim 1 , wherein the asymmetric reduction of 5-hydroxy-2-pentanone represented by formula (1) is catalyzed by an enzyme comprising the amino acid sequence of the reducing enzyme encoded by pNTRS of Escherichia coli HB101 (pNTRS) (FERM BP-08545), or pNTRGG1 of Escherichia coli HB101 (pNTRGG1) (FERM BP-7858).
3. The process according to claim 1 , wherein 5-hydroxy-2-pentanone represented by said formula (1) produced by hydrolyzing 2-acetyl-γ-butyrolactone represented by formula (5):
in the presence of an acid is used as a starting material.