JP2003259891A - Method for producing dehydroabietic acid derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a dehydroabietic acid derivative having a high added value from dehydroabietic acid. <P>SOLUTION: This method for producing the dehydroabietic acid derivative is characterized by producing at least one dehydroabietic acid derivative selected from the group consisting of 7-oxodehydroabietic acid, 7-hydrodehydroabietic acid, and 15-hydroxy-7-oxodehydroabietic acid from dehydroabietic acid with plant cultured cells, Caragana chamlagu cultured cells. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a dehydroabietic acid derivative. The present invention more specifically relates to a method for producing a dehydroabietic acid derivative, which comprises producing a dehydroabietic acid derivative from dehydroabietic acid using plant cultured cells.

[0002]

Dehydroabietic acid is obtained in large quantities from natural pine resin. Dehydroabietic acid is a substance industrially useful as a sizing agent for papermaking and the like, but it is expected to be converted into a drug having a well-established structure and a higher added value. That is, 7-oxodehydroabietic acid obtained from dehydroabietic acid, 7
Dehydroabietic acid derivatives such as -hydroxydehydroabietic acid and 15-hydroxy-7-oxodehydroabietic acid are extremely useful as perfumes and intermediates for pharmaceuticals and the like.

The inventors of the present invention have previously described useful products such as unsaturated ketones and epoxidized alcohols, which are used as intermediates for fragrances, pharmaceuticals, agricultural chemicals, etc., from cyclic olefins, using cultured cells of Muresume which are cultured cells of plants. Has been proposed (Japanese Unexamined Patent Publication No. 2001-252089). By the way, as described above, dehydroabietic acid, which is obtained in large amounts from natural pine resin, is expected to be converted into a drug having a well-established structure and higher added value, and 7-oxodehydroabieticin obtained from dehydroabietic acid in particular Acid, 7
Dehydroabietic acid derivatives such as -hydroxydehydroabietic acid and 15-hydroxy-7-oxodehydroabietic acid are extremely useful as perfumes and intermediates for pharmaceuticals and the like.

[0004]

Therefore, an object of the present invention is to provide a dehydroabietic acid derivative having a higher added value from dehydroabietic acid. That is, the object of the present invention is to use dehydroabietic acid as a starting material, without using a conventional heavy metal catalyst containing an alkali metal, an alkaline earth metal, or a transition metal, and at room temperature under normal pressure in a water solvent. Under mild reaction conditions of 7-oxodehydroabietic acid, 7-hydroxydehydroabietic acid and 15-hydroxy-7-oxodehydroabietic acid, which are extremely useful as intermediate materials for perfumes and pharmaceuticals, It is to provide a manufacturing method to obtain.

As a result of various investigations, the present inventors have found that the use of a biocatalyst, the cultured cell of Astragalus membranaceus, makes it possible to oxidize dehydroabietic acid in an energy-saving and environmentally friendly manner without using a heavy metal oxidizing agent. I found that.

[0006]

[Means for Solving the Problems] Therefore, according to the present invention, by using cultured cells of Japanese aureus, 7-
Production of dehydroabietic acid derivative, characterized in that at least one dehydroabietic acid derivative selected from the group consisting of oxodehydroabietic acid, 7-hydroxydehydroabietic acid and 15-hydroxy-7-oxodehydroabietic acid is produced. Is the way.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below. According to the present invention, dehydroabietic acid (1) is used as a raw material, and cultured cells of wolves are used as a biocatalyst to carry out a culture reaction in an MS culture solution. 7-oxodehydroabietic acid (2), 7 which is extremely useful as an intermediate raw material of
Dehydroabietic acid derivatives such as -hydroxydehydroabietic acid (3) and 15-hydroxy-7-oxodehydroabietic acid (4) can be obtained. The reaction is performed according to the following reaction formula.

[0008]

[Chemical 1]

The raw material dehydroabietic acid can be obtained in large amounts from natural pine resin. The culture reaction in the MS culture medium is in the temperature range of 15 to 30 ° C., more preferably 20.
It is carried out at a temperature range of -25 ° C for a culture period of 5 to 16 days, more preferably 10 to 14 days.

In this culture reaction, 1 part of dehydroabietic acid as a raw material was added to 100 parts by weight of the biocatalyst on a weight basis.
It is added in the range of 20 to 20 parts by weight, and the addition is carried out under standing or with stirring, but it is more preferable to carry out with stirring.

[0011] The Murrezu cultivated cells, which are the plant cultured cells used in the present invention, are obtained by removing a part of the tissue or organ of the living body from the living body and growing it in a suitable culture medium (callus). chamlagu)
It can be prepared by inducing from leaves or stems and growing on MS solid medium.

[0012]

EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited thereto.

Example 1 To 100 ml of MS liquid medium, 4 g of Muresume culture cells were added and precultured for 2 days. Next, 60 mg of dehydroabietic acid as a raw material was added to this medium, and the temperature was 25 ° C.
Then, shaking culture was carried out for 21 days in the dark with gentle stirring. After the reaction was completed, the cultured cells were separated by filtration, ether was added to the obtained filtrate, and solvent extraction was performed. The obtained extract was methylated with diazomethane, dehydrated by adding anhydrous sodium sulfate, and then the solvent was distilled off. The obtained crude reaction product was separated by silica gel column chromatography. Confirm the structure of the product from the spectral data,
The substance was identified.

The results of substance identification were as follows. <Methyl-7-oxodehydroabietate> m / z; 32
8.2035 (C_{twenty one}H₂₈O₃), IR; 1716cm^-1(C = O), 1
674 cm^-1(C = O), 1604cm^-1(C = C), 1H-N
MR; 1.24 (3H, CH₃), 1.26 (6H, CH₃), 1.34 (3
H, CH₃), 3.65 (3H, CH₃), 13 C-NMR; 177.84
(COOCH₃), 198.59 (C = O) <Methyl-7β-hydroxydehydroabietate> m /
z; 330.2196 (C_{twenty one}H₃₀O₃), IR; 3348 (OH), 1712c
m^-1(C = O), 1600cm^-1(C = C), 1H-NMR; 1.2
4 (3H, CH₃), 1.28 (3H, CH₃), 1.56 (6H, C
H₃), 3.66 (3H, CH ₃), 4.86 (1H, CH-OH), 13C-NM
R; 70.7 (CH-OH), 178.7 (COOCH₃) <Methyl-15-hydroxy-7-oxodehydroabiete
G> m / z; 344.1983 (C_{twenty one}H₂₈O_Four), IR; 3350 cm
^-1(OH), 1720cm^-1(C = O), 1664cm^-1(C = O),
1620 cm^-1(C = C), 1H-NMR; 1.25 (3H, C
H₃), 1.27 (3H, CH₃), 1.60 (3H, CH₃), 1.61 (3
H, CH₃), 3.65 (3H, CH₃), 13 C-NMR; 83.6 (C-O
H), 177.8 (COOCH₃), 198.3 (C = O)

Product yield 7-oxodehydroabietic acid (22%) and 7-hydroxydehydroabietic acid (13%) and 15-hydroxy-7-oxodehydroabietic acid (13%)
was gotten.

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Claims (3)

[Claims] 1. Using a cultured cell of Muresume, which is a plant cultured cell, selected from the group consisting of dehydroabietic acid to 7-oxodehydroabietic acid, 7-hydroxydehydroabietic acid and 15-hydroxy-7-oxodehydroabietic acid. A method for producing a dehydroabietic acid derivative, which comprises producing at least one dehydroabietic acid derivative as described above. 2. The dehydroabietic acid derivative is 7-
The method for producing a dehydroabietic acid derivative according to claim 1, which is a mixture of oxodehydroabietic acid and 7-hydroxydehydroabietic acid. 3. The method for producing a dehydroabietic acid derivative according to claim 1, wherein 15-hydroxy-7-oxodehydroabietic acid is obtained by hydroxylating the 15-position of dehydroabietic acid.