Kyowa Hakko Kogyo Co., Ltd.

Yukihiro Kuge

Takayuki Uwajima

Kenichi Mochida

Shinji Tomioka

Toru Sugaya

Tamotsu Eguchi

Takashi Oshiro

The present invention relates to a process for producing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid compounds or salts thereof represented by the following formula (II): ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 independently represent hydrogen, hydroxy or lower alkoxy, and R.sup.4 represent hydrogen, lower alkyl, aryl or aralkyl, the process comprising, allowing phenylalanine compounds to react with formaldehyde or paraformaldehyde in the presence of sulfuric acid or hydrobromic acid, the phenylalanine compounds being represented by the following formula (I): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meaning as defined above.

Process for producing tetrahydroisoquinoline-3-carboxylic acid compounds

The invention relates to a process for producing L(-)-tetrahydrofolic acid which comprises allowing dihydrofolate reductase to act upon dihydrofolic acid in the presence of (1) NADP or NADPH, and (2) glucose and glucose dehydrogenase. L(-)-tetrahydrofolic acid is useful as the intermediate for L(-)-leucovarin.

Process for producing L(-)-tetrahydrofolic acid

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Osakasayama, Japan

Yukihiro Kuge