JP2012097058A - Method of producing antioxidant active substance of rosemary - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently produce carnosol and its derivative which is one of the main antioxidant active substances of lamiaceous herbs such as rosemary and sage, by using a tree ingredient of Chamaecyparis pisifera and the like as a raw material.SOLUTION: The antioxidant active substance of the rosemary, carnosol and its derivatives are efficiently produced in a one-pot process directly from pisiferic acid through the following process. The process includes; oxidizing pisiferic acid which is a vegetable component of Chamaecyparis pisifera and the like, as a raw material with 2-iodoxy benzoic acid (denoted by IBX); and leaving a reaction product to stand at room temperature without separating the reaction product, so that a lactonization reaction and the like between a carboxylic acid and quinone methide in molecules of the product can progress.

Description

The present invention relates to a method for producing rosemary antioxidant active substance, and more particularly to a method for producing carnosol, which is one of rosemary antioxidant active substances, using raw materials such as Sawara. .

Lamiaceae plants are widely distributed throughout the world, about 200 genera and 3500 species are known. Among them, rosemary, sage, perilla, oregano, basil, thyme, marjoram, which have been used for a long time as herbs and medicines. It is known that Lamiaceae plants and the like contain an antioxidant active substance. These antioxidant active substances are roughly classified into four types: phenolic diterpenes, caffeic acid derivatives, flavonoids, and biphenyl derivatives.

Among the Lamiaceae plants, rosemary has long been known as a spice for meat dishes and a folk medicine, and it is widely known that it contains a strong antioxidant active component typified by carnosic acid, carnosol, and rosmanol ( Non-patent document 1). In recent years, for carnosic acid, antibacterial activity, cranial nerve cell death prevention effect, treatment / prevention effect of encephalemia, Alzheimer's disease prevention effect, fat absorption prevention effect, anti-inflammatory action, blood sugar level lowering effect in diabetics, whitening effect, etc. Various activities have been reported, and it has been reported that carnosol also exhibits various activities such as a biological defense mechanism activation action, a detoxification effect, a deodorizing effect, and a bactericidal action. About these antioxidant active substances, the utilization as a food additive, a supplement, a pharmaceutical, etc. is examined (patent document 1, nonpatent literature 2 thru | or nonpatent literature 4).

For example, a neurite elongation agent containing a plant-derived extract such as rosemary and sage as an active ingredient is disclosed (Patent Document 2). It is disclosed that the above-mentioned extracts carnosic acid and carnosol can be obtained from an alcohol extract at a predetermined site such as rosemary. However, the carnosic acid separated from the 5000 gram alcohol extract of rosemary leaves is 1.5 gram and carnosol is 1 gram, and there is an inexpensive method for producing carnosic acid and carnosol in a large amount. There is a problem that it is not. (Patent Document 3 and Patent Document 4).

Sawara, on the other hand, is a Japanese conifer and is naturally distributed in Tochigi, Gunma, Gifu and Nagano prefectures. The leaves contain a large amount of piciphenyl acid and related compounds (Non-patent Document 5). Piciphenyl acid has the same carbon skeleton as carnosic acid, is structurally similar, and differs only in that the phenolic hydroxyl group is one less than carnosic acid.

Previously, the present inventors invented a method for efficiently producing carnosic acid by extracting and separating piciferin acid from Sawara leaves in a high yield (Patent Documents 5 and 6).

Regarding carnosol, which is one of rosemary's antioxidant active substances, there has been known a method of producing carnosol by oxidizing it from carnosic acid separated and purified from rosemary with an oxidizing agent such as silver oxide. In this method, not only the yield of carnosic acid from rosemary is low, but the subsequent oxidation reaction of carnosic acid produces other by-products together with carnosol, and the separation and purification of carnosol is complicated.

Problems to be solved by the invention

By improving the method for producing carnosic acid described in [0006] above, carnosol is efficiently produced from picipheric acid in one pot.

In addition, this patent applicant discloses the following technical literature as a publication in which the literature well-known invention relevant to this invention was described.
JP 2001-158745 A JP 2007-230945 A Special table 2001-518072 gazette JP 2003-55686 A Japanese Patent Application No. 2008-150882 Japanese Patent Application No. 2008-31727 Zenta Tada, “Physiological activity of antioxidant active substances in Lamiaceae herbs”, FFI Journal of Japan, 2000, No. 184 S. C. Etter, Spices & Medicinal Plants, Journal of Herbs, 11, 121-159 (2004). T.A. Satoh, K .; Kosaka, K .; Itoh, A .; Kobayashi, M .; Yamamoto, Y. et al. Shimojo, C.I. Kitajima, J. et al. Cui, J .; Kamins, S .; Okamoto, M .; Izumi, T .; Shirasawa, S .; A. Lipton, J.M. Neurochem. , 104, 1161-1131 (2008) K. Ninomiya, H .; Matsuda, H .; Shimoda, N .; Nishida, N .; Kasajima, T .; Yoshino, T .; Morikawa, M .; Yoshikawa, Bioorg. Med. Chem. Lett. , 14 (8), 1943-1946 (2004) du Xiao, M .; Kuroyanagi, T .; Itani, H .; Tatsuura, M .; Udayama, M .; Murakami, K .; Umehara, N .; Kawahara, Chem. Pharm. Bull. 49 (11), 1479-1481 (2001).

Means for solving the problem

The inventors previously used carnosine, which is a strong antioxidant active ingredient of rosemary, by oxidizing the ortho position of phenol of a compound such as piciferin acid, which is an extract thereof, with a specific oxidizing agent. It discovered that an acid and its derivative could be manufactured (patent documents 5 and patent documents 6). This time, by improving the above-described invention, it was discovered that carnosol, one of rosemary's antioxidant active ingredients, can be directly produced in one pot from piciferic acid, the main component of Sawara, and the invention was completed.

（上記一般式［化１］において、Ｒ_１は、ＣＯＯ Ｒ_３、ヒドロキシメチル基、アルデヒド基のいずれかであり、Ｒ_２及びＲ_３は、それぞれ独立に水素原子または炭素数１ないし６のアルキル基を表す。）
下記一般式［化２］ないし一般式［化３］で表されるいずれかの酸化剤、

（上記一般式［化２］においてＸはベンゼン環のいずれかの位置に結合した水素、ハロゲン、アルキル基、アロコキシル基のいずれかを表す。［化３］においてＲ_４は、水素原子または炭素数１ないし６のアルキル基、アリル基、フェニル基、ハロゲン化フェニル基、ハロゲン化アルキル基のいずれかを表す。Ｘはベンゼン環のいずれかの位置に結合した水素、ハロゲン、アルキル基、アロコキシル基のいずれかを表す。）を、反応させることにより、酸化する第１の工程と、前記第１の工程後、反応混合物を放置し、ラクトンを生成させる第２の工程を有することを特徴とする下記一般式［化４］で表されるローズマリーの抗酸化活性物質の製造方法。

［２］前記サワラ属樹は、サワラであることを特徴とする［１］に記載のローズマリーの抗酸化活性物質の製造方法。
［３］前記酸化剤が、一般式［化２］において、Ｘ＝Ｈである２−ヨードキシ安息香酸（ＩＢＸと言う）であることを特徴とする［１］に記載のローズマリーの抗酸化活性物質の製造方法。
［４］前記酸化剤が、一般式［化３］で表される２−ヨードキシ安息香酸トリアシルエステル誘導体であることを特徴とする［１］に記載のローズマリーの抗酸化活性物質の製造方法。
［５］［１］ないし［４］の何れかに記載の製造方法により、製造したローズマリーの抗酸化活性物質。The present invention is composed of the following technical matters. That is,
[1] extracted from the species of the genus Sawara,
A piciferin acid derivative represented by the following general formula [Chemical Formula 1];

(In the above general formula [Chemical Formula 1], R ₁ is any one of COO R ₃ , a hydroxymethyl group, and an aldehyde group, and R ₂ and R ₃ are each independently a hydrogen atom or an alkyl having 1 to 6 carbon atoms. Represents a group.)
Any one of the following oxidants represented by the following general formula [Chemical Formula 2] to [Chemical Formula 3]:

(In the above general formula [Chemical Formula 2], X represents any of hydrogen, halogen, alkyl group, and aralkoxyl group bonded to any position of the benzene ring. In [Chemical Formula 3], R ₄ represents a hydrogen atom or a carbon number. 1 to 6 represents an alkyl group, an allyl group, a phenyl group, a halogenated phenyl group, or a halogenated alkyl group, and X represents a hydrogen, halogen, alkyl group, or aralkoxyl group bonded to any position of the benzene ring. Which represents any one of the following: a first step of oxidizing by reacting, and a second step of leaving a reaction mixture after the first step to produce a lactone A method for producing an antioxidant active substance of rosemary represented by the general formula [Chemical Formula 4].

[2] The method for producing an antioxidant active substance of rosemary according to [1], wherein the Sawara genus tree is Sawara.
[3] The antioxidant activity of rosemary according to [1], wherein the oxidizing agent is 2-iodoxybenzoic acid (referred to as IBX) in which X = H in the general formula [Chemical Formula 2] A method for producing a substance.
[4] The method for producing a rosemary antioxidant active substance according to [1], wherein the oxidizing agent is a 2-iodoxybenzoic acid triacyl ester derivative represented by the general formula [Chemical Formula 3] .
[5] A rosemary antioxidant active substance produced by the production method according to any one of [1] to [4].

The invention's effect

According to the present invention, carnosol, which is an antioxidant active substance of rosemary, can be produced easily and in large quantities from Sawara.

Hereinafter, embodiments of the present invention will be described in detail.

(For trees such as Sawara)
The raw material used in the method for producing the rosemary antioxidant active substance of the present invention contains, as its component, piciphenyl acid and its derivative, which are raw materials such as carnosol, which is the target substance of the production method of the present invention. Well, although not particularly limited, for example, a tree belonging to the genus Sarawra of the cypress family can be exemplified. Examples of the tree include Sawara, Shinobu hiba, Ogon Shinobu hiba, Himuro and Hiyoku hiba. Among the above-mentioned examples of conifers, Sawara is preferable from the viewpoint of production and handling, and these raw materials can be mixed and used. Hereinafter, general formulas of piciphenyl acid and its derivatives, which are starting materials for the antioxidant active substance of rosemary, which is the target substance of the production method of the present invention, are shown.

In the general formula [Chemical Formula 1], R ₁ is any one of COOR ₃ , a hydroxymethyl group, and an aldehyde group. That is, R ₁ is a carboxyl group, a carboxylic ester group, a hydroxymethyl group, or an aldehyde group.

R ₂ and R ₃ are each independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. Examples of the alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, an n-propyl group, and an i-propyl group. Examples thereof include a group, an n-butyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, and an n-hexyl group.

In the general formula [Chemical Formula 1], when R ₁ is a carboxyl group (R ₁ = COOH) and R ₂ is a hydrogen atom (R ₂ = H), it becomes piciferic acid. Piciferic acid is the most abundant diterpene in Sawara, and is a chemically stable, colorless, odorless crystal.

Sawara is an evergreen tree that can be found all over Japan. It is a biomass that can be obtained very easily and exists in large quantities. In addition, in this invention, it is preferable to use the leaf which contains many piciferin acid and its derivative compound in a part of a sawara.

A method for extracting piciferin acid or the like from a raw material such as sawara is not particularly limited, and for example, it can be extracted by the following method. That is, it can be easily extracted by immersing a raw material such as sawara in a solvent or refluxing with a solvent. Examples of the solvent that can be used include alcohols, alkanes, carboxylic acids, esters, and ketones. In addition, these solvents can be used alone, or two or more of these solvents can be appropriately mixed and used.

Examples of the alcohol include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl 1-propanol, t-butyl alcohol, 1-pentanol, 2-pentanol, and 3-pen. Examples include butanol, 2-methyl 1-butanol, 3-methyl 1-butanol, 2,2dimethyl 1-propanol and the like. Examples of the alkane include pentane, hexane, heptane, octane, nonane and decane.

Examples of the ketone include acetone, methyl ethyl ketone (MEK), and diethyl ketone. In addition, if necessary, two or more kinds of the above organic solvents can be adopted and used as a mixed solution. Among the above solvents, from the viewpoint of handling such as safety, it is preferable to use an alcohol alone or a mixed solvent of water and alcohol. It is particularly preferable to use a mixed solvent of water and ethanol.

The extraction time and extraction temperature when performing the solvent extraction can be appropriately set depending on the solvent to be extracted. For example, when the raw material is sawara and methanol is extracted as the solvent to be extracted, the extraction temperature is preferably set to the reflux temperature, and the extraction reaction time can be 10 to 24 hours. By the above extraction method, a solution containing piciferic acid represented by the following general formula and its derivative can be extracted, concentrated, and purified by column chromatography.
(Manufacture of rosemary antioxidant active substances)

The method for producing an antioxidant active substance of rosemary of the present invention comprises extracting and separating piciferin acid and its derivative from a tree such as Sawara, oxidizing the ortho position of phenol such as piciferin acid with peroxide, and oxidizing product It is characterized by having a step of allowing a lactonization reaction by leaving it for a required time without separation.

In the present invention, rosmanol, isorosmanol, carnosic acid, etc., which are rosemary's other antioxidant active substances, may be produced together with carnosol by changing the time, temperature and solvent after oxidation of picipheric acid. .
In this reaction, the ratio and yield of these products vary depending on the conditions such as the time, temperature, solvent, etc., which are allowed to stand after the oxidation reaction. In the present invention, "rosemary antioxidant active substance" does not refer to those extracted only from rosemary, but as a starting material, Lamiaceae plants other than rosemary such as sage, perilla, oregano, basil, Or the composition manufactured by using as a starting material what combined these starting materials is included.
(Ortho-position oxidation and lactonization reaction of piciferic acid)
According to the method for producing rosemary antioxidant active substance of the present invention, a specific peroxide represented by the following general formula is represented in the structural formula of picipheric acid represented by the above chemical formula and derivatives thereof in the ortho-oxidation reaction of phenol. Characterized by the points adopted. That is, in the present invention, an oxidizing agent represented by the following general formula is used to oxidize the ortho position of phenol in piciferic acid and its derivatives, and the reaction product is lactonized to obtain carnosol.

（上記一般式中［化２］において。Ｘはベンゼン環のいずれかの位置に結合した水素、ハロゲン、アルキル基、アロコキシル基のいずれかを表す。また、［化３］において、また、Ｒ_４は、それぞれ独立に水素原子または炭素数１ないし６のアルキル基、アリル基、フェニル基、ハロゲン化フェニル基、ハロゲン化アルキル基のいずれかを表す。Ｘはベンゼン環のいずれかの位置に結合した水素、ハロゲン、アルキル基、アロコキシル基のいずれかを表す。）

(In the above general formula, in [Chemical Formula 2], X represents any of hydrogen, halogen, an alkyl group, and an alkoxyl group bonded to any position of the benzene ring. In [Chemical Formula 3], R ₄ Each independently represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, an allyl group, a phenyl group, a halogenated phenyl group, or a halogenated alkyl group, and X is bonded to any position of the benzene ring. (Represents any of hydrogen, halogen, alkyl group, and aralkoxyl group.)

In general, the methods employed in the ortho-position oxidation reaction of phenols include a direct oxidation method using selenium oxide, an oxidation using benzoyl peroxide, an air oxidation, and 2-iodoxy benzoic acid (hereinafter referred to as “IBX”). A method such as oxidation by the method can be exemplified.

The above IBX, which is an oxidizing agent used in the present invention, can be easily produced from 2-iodobenzoic acid under predetermined conditions. The reaction formula is shown below.

The orthoquinone produced after oxidation by IBX is in an equilibrium relationship with quinone methide. When this is allowed to stand after this oxidation reaction, the lactonization reaction proceeds between carboxylic acid and quinone methide, and carnosol is produced in one pot. The reaction time and temperature are not particularly limited to those described in the examples.

In the present invention, carnosol can be produced directly from picipheric acid by using IBX as an oxidizing agent and leaving the generated equilibrium mixture of orthoquinone and quinone metide to allow the lactonization reaction from quinone methide to proceed. The reaction formula is shown below.

Thus, according to the production method of the present invention, carnosol and its derivative rosemary antioxidant active substance can be produced easily and easily in large quantities. Furthermore, useful compounds such as isorosmanol and rosmanol can be produced from these antioxidant active substances.

Hereinafter, although the present invention is explained using an example, the present invention is not limited to these at all.

<Separation of piciferic acid>
Sawara leaves (collected from the forest of Tokyo University of Agriculture and Technology, Harumi-cho, Fuchu-shi, Tokyo) were collected and used as starting materials without drying. 450 g of fresh leaves of the above Sawara were weighed and refluxed in about 1.6 L of methanol at about 65 ° C. for 24 hours. Next, the methanol extract obtained by the above refluxing operation was concentrated under reduced pressure, and then a liquid / liquid extraction operation was performed with ethyl acetate and water. Further, after the above extraction operation, the ethyl acetate layer was concentrated, and the concentrate was subjected to column chromatography using silica gel and hexane / ethyl acetate (volume ratio 3: 1). After concentrating the fraction containing piciferin acid, column chromatography is performed again in the same manner, and the resulting fraction containing piciferin acid is crystallized using hexane / ethyl acetate (volume ratio 3: 1) to obtain the target compound. 2.0 g of some piciferic acid was obtained.

The melting point, ¹ H-NMR, and ¹³ C-NMR of the generated piciferin acid were measured. In addition, the melting | fusing point measuring device used MEL-TEMP by Laboratory Device, and measured it on the conditions without correction | amendment. Measurement of ¹ H-NMR and ¹³ C-NMR was performed using a JEOL alpha-600 ( ¹ H: 600 MHz, ¹³ C: 150.8 MHz) spectrometer manufactured by JEOL Ltd. Tetramethylsilane in deuterated chloroform was used as a standard.

Piciferic acid: white crystals; m. p. : 174-180 ° C .; ¹ H-NMR (600 MHz, CDCl ₃ ) δ: 6.89 (1H, s), 6.67 (1H, s), 3.10 (1H, sept., J = 6.6 Hz) ), 2.89 (1H, dd, J = 16.2, 6.0 Hz), 2.82-2.76 (2H, m), 2.46 (1H, dddd, J = 13.1, 12. 0, 11.0, 5.9 Hz), 1.94 (1 H, m), 1.87 (1 H, ddd, J = 11.0, 4.4, 2.8 Hz), 1.60 (1 H, ddd) , J = 13.7, 3.4, 3.1 Hz), 1.49 (1H, dd, J = 13.2, 1.8 Hz), 1.45 (1H, d, J = 12.6 Hz), 1.24 (2H, m), 1.22 (3H, d, J = 6.6 Hz), 1.21 (3H, d, J = 6.6 Hz), 0.96 (3H, s), 0 ^{82 (3H, s); 13} C-NMR (150MHz, CDCl 3) δ: 181.2,150.6,138.2,133.5,129.2,127.4,112.3,52.2 47.5, 41.7, 36.7, 34.0, 32.1, 29.3, 26.8, 22.6, 22.3, 20.3, 20.1, 18.6.

<Production of 2-iodoxybenzoic acid (IBX)>
Dissolve potassium persulfate (DuPont brand name: Oxone) (37.2 g, 0.06 mol) in water (200 mL), add 2-iodobenzoic acid (5.0 g, 0.02 mmol), and add 2 at 90 ° C. Stir for hours. The reaction mixture was ice-cooled for 24 hours, and the crystals were filtered off with suction and washed with water (6 × 100 mL) and acetone (2 × 100 ml). The crystalline solid was dried at room temperature under reduced pressure to obtain IBX (3.4 g, 0.01 mmol) in a yield of 61%.

IBX; white powder; m. p. : 232-233 ° C .; ¹ H-NMR (600 MHz, d ₆ -DMSO) δ: 8.15 (1H, d, J = 7.8 Hz), 8.04 (1H, d, J = 7.2 Hz), 8.00 (1H, t, J = 7.9 Hz), 7.85 (1H, t, J = 7.8 Hz); ¹³ C-NMR (150 MHz, d ₆ -DMSO) δ; 167.49, 146. 55, 133.38, 132.95, 131.43, 130.08, 124.99

<Synthesis of carnosol>
Piciferic acid (2.0 g, 6.32 mmol) was dissolved in CHCl ₃ / MeOH (4: 1) (30 mL), IBX (2.1 g, 7.58 mmol) was added, and the mixture was stirred at room temperature under an argon stream for 24 hours. . After confirming the progress of the oxidation reaction by TLC, NaBH ₄ (240 mg, 6.32 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 0.5 hours under an argon stream. Thereafter, 1M HCl was added to stop the reaction, followed by liquid-liquid extraction with Hexane, and then the organic layer was washed with brine. Thereafter, it was dried over MgSO ₄ , concentrated, and purified by silica gel column chromatography (hexane: EtOAc = 10: 1) to obtain carnosol (1.2 g, 3.6 mmol) in a yield of 57%.

Carnosol: yellow powder; m. p. : 212-213 ° C .; ¹ H-NMR (600 MHz, CDCl ₃ ) δ: 6.64 (1H, s), 5.76 (1H, s), 5.37 (1H, dd, J = 3.6 Hz, 1.4 Hz), 5.31 (1 H, s), 3.09 (1 H, sept, J = 6.0 Hz), 2.91 (1 H, d, J = 12 Hz), 2.43, 2.40, 2.38 (1H, td, J = 4.2, 14 Hz), 2.23-2.19 (1H, m), 2.02-1.93 (1H, m), 1.87-1.85 (1H, m), 1.73 (1H, dd, J = 11,5.8 Hz), 1.32-1.26 (1H, m), 1.23 (3H, d, J = 6.0 Hz) , 1.22 (3H, d, J = 6.0 Hz), 0.90 (3H, s), 0.86 (3H, s); ¹³ C-NMR (150 MHz, CDCl ₃ ): 175.91, 141.78, 141.08, 132.83, 132.08, 121.58, 112.27, 77.88, 48.39, 45.43, 40.97, 34.49, 31.67, 29.71, 29.14, 27.27, 22.49, 22.44, 19.68, 18.86.

From the above examples, piriferric acid (Pisiferic acid) was isolated and purified from Sawara in high yield, and this was ortho-oxidized to obtain carnosol, one of the main antioxidant active substances of rosemary. It is understood that it can be manufactured efficiently.

In the above examples, the main antioxidant active substance of rosemary, which has been attracting attention in recent years because of its preventive effect on Alzheimer's disease and various lifestyle-related diseases, is supplied from the leaves of Sawara planted in large quantities as wood resources. The technical significance is extremely large.

<Measurement of antibacterial activity>
The results of measuring the anti-methicillin-resistant Staphylococcus aureus activity and the anti-acne fungus activity using the main antioxidant active substance of rosemary described in [Patent Document 6].

The main antioxidant active substance obtained by the method for producing rosemary antioxidant active substance of the present invention has a remarkable antibacterial activity, and these results indicate that the synthesized main antioxidant active substance of rosemary is It has the potential to be useful as an acne treatment.

The method for producing an antioxidant active substance of rosemary described in the present invention is a method for producing an antioxidant active substance using Sawara planted in large quantities as a wood resource. Can contribute. Furthermore, the method for producing carnosic acid of the present invention can greatly contribute to technological innovation in the fields of medicine and medical technology.

In the present invention, carnosol can be produced directly from picipheric acid by using IBX as an oxidizing agent and leaving the generated equilibrium mixture of orthoquinone and quinone metide to allow the lactonization reaction from quinone methide to proceed. In addition, in the case of lactonization after oxidation of picipheric acid, a metal salt such as silver carbonate or silver oxide or an acid such as pyridinium p-toluenesulfonate (PPTS) or zinc chloride can be added to promote the reaction. The reaction formula is shown below.

<Synthesis of carnosol>
Piciferic acid (2.0 g, 6.32 mmol) was dissolved in CHCl ₃ / MeOH (4: 1) (30 mL), IBX (2.1 g, 7.58 mmol) was added, and the mixture was stirred at room temperature for 1 hour under an argon stream. . After confirming the disappearance of picipheric acid by thin layer chromatography (TLC), silver carbonate (1.75 g, 6.32 mmol) was added, and the mixture was further stirred for 16 hours. Next, NaBH ₄ (240 mg, 6.32 mmol) was added and stirred at room temperature for 0.5 hour, and then the reaction was stopped by adding 1M HCl. After confirming that the mixture was acidic, liquid-liquid extraction was performed with chloroform. The organic layer was washed with brine, and then the extract was dried over MgSO ₄ and concentrated. The concentrated solution was purified by silica gel column chromatography (hexane: EtOAc = 10: 1) to obtain carnosol (1.3 g, 3.9 mmol) in a yield of 62%.

Claims (5)

Extracted from Sawara species
Piciferic acid represented by the following general formula [Chemical Formula 1] or a derivative thereof,

(In the above general formula [Chemical Formula 3], R ₁ is any one of COO R ₃ , a hydroxymethyl group, and an aldehyde group, and R ₂ and R ₃ are each independently a hydrogen atom or an alkyl having 1 to 6 carbon atoms. Any one of the oxidizing agents represented by the following general formula [Chemical Formula 2] to general formula [Chemical Formula 3],

(In the above general formula, X represents any one of hydrogen, halogen, an alkyl group, and an aralkoxyl group bonded to any position of the benzene ring.) In [Chemical Formula 3], R ₄ represents a hydrogen atom or It represents any of an alkyl group having 1 to 6 carbon atoms, an allyl group, and a phenyl group. X represents any of hydrogen, halogen, an alkyl group, and an aralkoxyl group bonded to any position of the benzene ring. ) And reacting with lactonization by leaving it at room temperature without separating the oxidized product, and efficiently producing rosemary's antioxidant active substance carnosol represented by the following general formula [Chem. 4] in one pot. Manufacturing method to synthesize.

The method for producing an antioxidant active substance of rosemary according to claim 1, wherein the Sawara genus tree is Sawara.   The oxidant is a oxidant of phenol containing 2-iodoxybenzoic acid represented by the general formula [Chemical Formula 2] and a related compound having a substituent on the benzene ring. A method for producing an antioxidant active substance. The method for producing a rosemary antioxidant active substance according to claim 1, wherein the oxidizing agent is a 2-iodoxybenzoic acid triacyl ester derivative represented by the general formula [Chemical Formula 3]. The antioxidant active substance of rosemary manufactured by the manufacturing method of any one of Claim 1 thru | or 4.