Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease
Reexamination Certificate
2001-02-28
2002-02-05
Saucier, Sandra E. (Department: 1651)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Transferase other than ribonuclease
C435S830000
Reexamination Certificate
active
06344351
ABSTRACT:
TECHNICAL FIELD
The present invention relates to optically active amino compounds having an aryl group and the like at the 1-position, which can be used as intermediates for pharmaceuticals and agricultural chemicals. 1-(3,4-Dimethoxyphenyl)-2-aminopropane, which is one of the desired compounds of the present invention, is an important compound as intermediates for CL316, 243 (J. D. Bloom et al.,
J. Med. Chem
. 35, 3081-3084 (1992)) and analogous compounds thereof, which are promising as antidiabetics and agents for antiobesity under development.
In addition, (S)-2-amino-1-methoxypropane, which is another desired compound is a useful compound which can be used as intermediates for herbicides.
BACKGROUND ART
Processes for preparing optically active amino compounds having an aryl group and the like at the 1-position by using an enzyme include a report in Nakamichi et al. (
Appl. Microbiol. Biotechnol
., 33, 634-640 (1990)) and Japanese Patent Examined Publication No. Hei 4-11194. It is disclosed in these publications that an (S)-form can be efficiently prepared by transferring an amino group to 1-(substituted phenyl)-2-propanones by using an enzyme. Further, Japanese Patent Examined Publication No. Hei 4-11194 also discloses a preparation of an (R)-form; however, the present inventors have conducted additional experiment to examine microorganisms and substrate disclosed in Japanese Patent Examined Publication No. Hei 4-11194 and found that the reproducibility by means of this method is very poor, and thereby making it difficult to use this method for practical purposes. Further, Stirling et al. disclose a method in which only the (S)-form is decomposed by actions of an &ohgr;-amino acid transaminase to a racemic amino compound produced by an organic reaction, to thereby obtain the remaining (R)-form (Japanese Patent Laid-Open No. Hei 3-103192). However, in this method, since the (S)-form is undesirably decomposed to obtain the (R)-form, the yield against the substrate is lowered to 50% or less. Accordingly, this method cannot be considered to be advantageous from the aspect of costs. In addition, Stirling et al., the authors as above, also disclose a method in which only (S)-amino compounds are prepared from a ketone-form by using an &ohgr;-amino acid transaminase in the presence of an amino donor. However, optically active (R)-amino compounds cannot be produced by this method.
DISCLOSURE OF INVENTION
Accordingly, an object of the present invention is to provide a method for preparing optically active (R)-amino compounds by actions of microbial enzymes efficiently and inexpensively.
The present inventors have found a microorganism from soil which can prepare optically active (R)-amino compounds with good yield by carrying out an amino group transfer to a ketone compound having an aryl group, and the like at 1-position (R)-form specifically and efficiently. This microorganism has been deposited at the National Institute of Bioscience and Human-Technology Agency of Industrial Science and Technology, located at 1-3, Higashi 1 chome Tsukuba-shi Ibaraki-ken 305, Japan, and has been given the depository designation number FERM BP-5228. Further studies have been made on the reaction using this microorganism, and the present invention has been completed.
Specifically, the present invention, in essence, pertains to:
[1] A method for preparing an optically active (R)-amino compound characterized by the method comprising stereoselectively carrying out amino group transfer by action of an (R)-form-specific transaminase in the co-presence of a ketone compound (amino acceptor) represented by the following general formula (I):
wherein n is 0 to 5; m is 0 or 1; and X represents an unsubstituted aryl group having 6 to 14 carbon atoms, an aryl group having 6 to 14 carbon atoms and having one or more substituents selected from the group consisting of an alkyl group having 4 to 15 carbon atoms, a hydroxyl group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a nitro group, a carboxyl group, and a trifluoromethyl group, or a methoxyl group, and is an amino compound (amino donor) of an achiral form, a racemic form, or an (R)-form represented by the general formula (II):
wherein X
1
and X
2
independently represent a hydrogen atom; a straight-chain alkyl group having 1 to 10 carbon atoms; a branched alkyl group having 5 to 12 carbon atoms; an unsubstituted aryl group having 6 to 14 carbon atoms; an aryl group having 6 to 14 carbon atoms and having one or more substituents selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a nitro group, and a carboxyl group; an aralkyl group having 7 to 16 carbon atoms and having one or more substituents selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a nitro group, and a carboxyl group; or a hydroxymethyl group or a hydroxyethyl group, to give an optically active (R)-amino compound represented by the general formula (IV):
wherein n, m, and X have the same definitions as those of n, m, and X in the general formula (I), respectively;
[2] The method for preparing an optically active (R)-amino compound described in item [1] above, characterized in that in the general formula (II), X
1
is an alkyl group having 2 to 10 carbon atoms, a phenyl group, or a naphthyl group, and X
2
is an alkyl group having 1 or 2 carbon atoms;
[3] The method for preparing an optically active (R)-amino compound described in item [1] above, characterized in that the amino donor represented by the general formula (II) is an alkyl ester of D-alanine, the alkyl group having 1 to 8 carbon atoms;
[4] The method for preparing an optically active (R)-amino compound described in item [1] above, wherein the amino donor represented by the general formula (II) is (R)-1-phenylethylamine, (R)-1-naphthylethylamine, (R)-1-methylpropylamine, (R)-2-aminopentane, (R)-2-amino-1-propanol, (R)-1-methylbutylamine, (R)-1-phenylmethylamine, (R)-1-amino-1-phenylethanol, (R)-2-amino-2-phenylethanol, (R)-3-aminoheptane, (R)-1-amino-3-phenylpropane, (R)-2-amino-4-phenylbutane, (R)-2-amino-3-phenylpropanol, (R)-3,4-dimethoxyaminopropane, (R)-1-methylheptylamine, benzylamine, (S)-2-phenylglycinol, 3-aminophenylbutane, L-phenylalaninol, (R)-2-amino-1-methoxypropane, D-alanine methyl ester, D-alanine ethyl ester, or a racemic compound thereof;
[5] The method for preparing an optically active (R)-amino compound described in any one of items [1] to [4] above, characterized in that in the general formula (I) and the general formula (IV), n and m are n=1 and m=0;
[6] The method for preparing an optically active (R)-amino compound described in any one of items [1] to [5] above, characterized in that in the general formula (I) and the general formula (IV), X is phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-trifluoromethylphenyl, or methoxyl;
[7] The method for preparing an optically active (R)-amino compound described in any one of items [1] to [6] above, characterized in that the amino acceptor represented by the general formula (I) and the amino donor represented by the general formula (II) are brought into contact with a culture of microorganisms, separated bacterial cells, treated bacterial cells, or immobilized bacterial cells which produce (R)-form-specific transaminases;
[8] The method for preparing an optically active (R)-amino compound described in any one of items [1] to [6] above, characterized in that the amino acceptor represented by the general formula (I) and the amino donor represented by the general formula (II) are brought into contact with cell-free extracts of microorganisms, crudely purified enzymes, pur
Hasegawa Junzo
Ikenaka Yasuhiro
Iwasaki Akira
Kizaki Noriyuki
Ogura Masahiro
Birch & Stewart Kolasch & Birch, LLP
Kaneka Corporation
Saucier Sandra E.
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