Daicel Chemical Industries, Ltd.

Takeshi Ishiguro

Akinobu Matsuyama

Noritsugu Yamasaki

Kiyoshi Ikura

Michio Ito

Hidekazu Akamatsu

Takayuki Abe

Kazuaki Furukawa

Katsuya Miki

Kenichiro Miyazawa

Provided is a method of manufacturing target substances with use of supercritical fluid chromatography, by which the following are achieved: solution of a problem at the time of sequential injections of samples containing the target substances; an increase of a treatment amount of separation per unit time; and improvement of efficiency in separation. The method includes the steps of: injecting the sample containing the target substances into a mobile phase; and returning composition of the mobile phase to a pre-change state after changing the composition of the mobile phase. The step of returning the composition of the mobile phase to the pre-change state after changing the composition of the mobile phase is performed during a period of time from detection of a peak of one of the target substances which is eluted latest from a column among the target substances separated by the supercritical fluid chromatography apparatus to injection of the next sample, whereby the problem is solved.

Method of manufacturing substances by supercritical fluid chromatography

An (R)-2-amino-1-phenylethanol derivative shown by the general formula (IIa) ##STR1## wherein R.sup.1 and R.sup.5 represent a hydrogen atom, etc.; R.sup.2, R.sup.3 and R.sup.4 independently represent a halogen atom, etc., or a salt thereof, can readily be produced (1) by permitting a microorganism belonging to the genus Rhodosporidium, the genus Comamonas or the like to act on a mixture of corresponding (R)-form and (S)-form to asymmetrically utilize, or (2) by permitting a microorganism belonging to the genus Lodderomyces, the genus Pilimelia or the like to act on a corresponding aminoketone derivative to asymmetrically reduce. An (R,R)-1-phenyl-2-�(2-phenyl-1-alkylethyl) amino!ethanol derivative having a high optical purity can easily be obtained from the compound of the formula (IIa) or a salt thereof. Said derivative is useful as an intermediate for producing an anti-obesity agent and so on.

Processes for producing optically active 2-amino-1-phenylethanol

An (R)-2-amino-1-phenylethanol derivative shown by the general formula (IIa) ##STR1## wherein R.sup.1 and R.sup.5 represent a hydrogen atom, etc.; R.sup.2, R.sup.3 and R.sup.4 independently represent a halogen atom, etc., or a salt thereof, can readily be produced (1) by permitting a microorganism to act on a mixture of corresponding (R)-form and (S)-form to asymmetrically utilize, or (2) by permitting a microorganism to act on a corresponding aminoketone derivative to asymmetrically reduce. An (R,R)-1-phenyl-2-[(2-phenyl-1-alkylethyl) amino]ethanol derivative having a high optical purity can easily be obtained from the compound of the formula (IIa) or a salt thereof. Said derivative is useful as an intermediate for producing an anti-obesity agent.

Production of optically active 2-amino-1-phenylethanol derivatives by

Growing community of inventors

Nakakubiki-gun, Japan

Takeshi Ishiguro