JP2720176B2 - Method for producing panaxacols - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to panax ginseng (Panax.ginseng CAMeye).
The present invention relates to a novel method for synthesizing a diyne compound dihydropanaxacol extracted from the root or callus of r) and related compounds.

(Prior art) Conventionally, as cancer chemotherapeutic agents, alkylating agents (nitrogen mustards, ethyleneimines, sulfonic esters), antimetabolites, (folate antagonists, purine antagonists, pyrimidine antagonists), Plant fission toxins (colcemid, vinblastine, etc.), antibiotics (sarcomycin,
Cartinophilin, mitomycin, etc., hormones (adrenal steroids, male hormones, female hormones), porphyrin complex salts (murphyrin, COPP) and the like are used.

However, most of them are cytotoxic substances and exhibit serious side effects. Therefore, development of anticancer agents having low toxicity and excellent anticancer activity has been desired.

In view of the above, the present inventors have conducted a search for a substance having a low toxicity and an anticancer activity from a wide range of animals, plants and microorganisms, and as a result, a novel substance extracted from the roots of Panax ginseng or its callus. The diyne compound was found to have excellent anticancer activity and extremely low toxicity, and a patent application was filed for this invention (Japanese Patent Application No. 61-50067).

However, there is a problem that the in vivo activity test cannot be performed because the content of the polyacetylene derivative in the callus is low.

(Problems to be Solved by the Invention) Accordingly, an object of the present invention is to enable supply of a large amount of a polyacetylene derivative by chemical synthesis.

(Means for Solving the Problems) The inventor of the present invention is able to synthesize the desired dihydropanaxacol and its analogous compounds in a stereoselective and high-yield manner by selecting tartar tartrate as a raw material for synthesis. And solved the above problem.

That is, the present invention relates to the compound (A) (Wherein R ¹ represents ^one of a tetrahydropyranyl group and a trialkylsilyl group) and the compound (B) (Wherein R ² represents any one of a tetrahydropyranyl group and a trialkylsilyl group, and R ³ represents an ethyl group.) In the presence of a base to give a compound (C) (Wherein R ¹ and R ² each represent either a tetrahydropyranyl group or a trialkylsilyl group, and R ³ represents an ethyl group.). ) An object of the present invention is to provide a method for producing the same.

Dihydropanaxacol, a typical compound synthesized by the method of the present invention, is described in JP-A-62-207234.
Compounds described in Examples on page 223, having the following formula Compound (1) represented by the formula (4,6-heptadecadiin-3,
9,10-triol) and has the following physicochemical properties.

(A) Form of substance: colorless oily substance The present invention is characterized in that dihydropanaxacol having such a characteristic diyne structure and its analogous compound are synthesized from two components.

That is, for example, in the case of dihydropanaxacol (I), It is characterized by being synthesized from components obtained from a propanol part and a diyne part, and components obtained from a glycol part and a hexyl part.

Taking the synthesis method of dihydropanaxacol as an example, a preferred embodiment of the synthesis method of the present invention using L-tartaric acid diethyl ester as a raw material is shown in the following scheme.

Each reaction shown in the above scheme will be described in detail below.

(A) Synthesis of ketal (2) The tartaric acid ester used as a raw material may be either an ester of L-tartaric acid or an ester of D-tartaric acid, depending on the configuration of the tartaric acid ester used and the configuration of the last dihydropanaxacol. The configuration of the final dihydropanaxacol is determined. When an ester of D-tartaric acid is used, the configuration of the glycol moiety of the obtained dihydropanaxacol is the same as that of natural panaxacol. As the ester, other than an alkyl ester, an ester such as benzyl may be used.
The esters may not be derived from the same alcohol. That is, an asymmetric tartaric acid ester can be used. In particular, L-(+)-tartaric acid diethyl ester or D-
It is preferred to use (-)-tartrate diethyl ester.

Examples of the reagent that can be used for ketalization include cyclohexanone, acetone, and methyl ethyl ketone, and it is particularly preferable to use acetone dimethyl acetal. When an acid catalyst is used, camphorsulfonic acid (CSA), paratoluenesulfonic acid (T
sOH), pyridinium paratoluenesulfonate (PPT)
S) and the like can be used. As the solvent, a solvent used for normal ketalization, for example, benzene, toluene, etc. can be used, but it is not necessary to use a solvent, and usually 20 ° C.
The reaction may be performed in a range of 150 ° C.

By using the above conditions, the ketal compound (2) can be usually obtained in a yield of 90% or more.

(B) Synthesis of diol (3) In order to convert diester (2) to diol (2), lithium aluminum hydride (LiAlH ₄ ), lithium borohydride, and the like are used in an anhydrous solvent such as anhydrous ether or anhydrous tetrahydrofuran (THF). The reaction may be carried out usually with an ester reducing agent such as (LiBH ₄ ) at −20 ° C. to 50 ° C., and the desired compound (3) can be obtained usually with a yield of 80% or more.

(C) Introduction of a leaving group ((3) → (4)) Paratoluenesulfonyl group (p-Ts group), methanesulfonyl group (Ms group) suitable as a leaving group for diol (3)
To introduce the corresponding paratoluenesulfonyl chloride (p-TsCl) or methanesulfonyl chloride (Ms
The corresponding chlorides such as Cl) may be reacted with 1.0 mol to 1.2 mol, preferably 1 mol, with respect to (3),
A leaving group can be selectively introduced into one hydroxyl group of (3). Using pyridine, collidine or the like as a solvent,
By reacting at 5 ° C. to 25 ° C. for 5 hours, the desired (4) can be obtained with almost no by-products reacted with both hydroxyl groups.

(D) Introduction of a protecting group ((4) → (5)) The unreacted hydroxyl group in the compound (4) is preferably protected by a commonly used hydroxyl protecting group. Protecting groups that can be used include protecting groups that readily provide a hydroxyl group in the presence of an acid, such as a tetrahydropyranyl group (THP
Group), a trialkylsilyl group and the like.
To introduce a protective group, dihydropyran (DHP) or trialkylsilyl chloride may be reacted with (4) as a corresponding compound, and CAS or the like may be used as an acid catalyst in the reaction. The desired hydroxyl-protected compound (5) can be obtained by reacting the mixture at 0 ° C. to 25 ° C. using dichloromethane, chloroform or the like as a solvent.

When a THP group is introduced as a protecting group, the resulting (5) becomes a mixture of diastereomers due to the presence of an asymmetric carbon in the THP group, but the subsequent reaction can proceed as it is. it can.

(E) Hexylation ((5) → (6)) Compound (5) is n-hexylated by a nucleophilic reaction,
Hexyl compound (6) can be obtained. Reagents that can be used for hexylation include n-hexyl copper lithium,
Metal hexyl compounds such as n-hexyllithium can be mentioned. These reagents can be reacted at -20 ° C to 0 ° C in an anhydrous solvent such as anhydrous ether or anhydrous THF, preferably under a stream of an inert gas such as nitrogen.
Particularly preferred hexylating agents include lithium n-hexylcopper, but the reagent is preferably prepared at the time of use.

(F) Synthesis of triol (7) Triol compound (7) from hexylated compound (7)
The reaction may be carried out in a solvent such as methanol or ethanol in the presence of an acid such as hydrochloric acid, sulfuric acid or paratoluenesulfonic acid. The reaction is usually carried out at
By performing for 1.0 hour, (7) can be obtained in good yield.

(G) Introduction of Leaving Group ((7) → (8)) As the suitable group as the leaving group, the leaving groups described in (c) above can be used, and they are obtained by the above-mentioned reagent. Can be easily introduced. Reagent volume
By leaving the mixture at 1.0 mol to 1.2 mol and reacting at 0 to 25 ° C. for 5 hours, a leaving group can be selectively introduced into the terminal hydroxyl group, whereby (8) can be obtained.

(H) Epoxy-alcohol (9) The epoxy alcohol derivative (9) can be obtained by treating the compound (8) with a base such as anhydrous potassium carbonate or anhydrous sodium carbonate in a solvent such as methanol or ethanol. The reaction is carried out at a reaction temperature of usually 0 ° C. to 30 ° C. for about 1 hour to obtain (9) in a yield of about 90% or more.

(Ii) Introduction of a protecting group ((9) → (10)) In the obtained (9), it is preferable to protect a hydroxyl group, but the protecting group described in (d) is preferably used as the protecting group. Can. The protecting group can be introduced by the method described above, and the protected hydroxyl group (10) can be obtained.

(Nu) Diyne compound (13) and protected form (14) A diyne compound can be obtained from diacetylene (12) and propionaldehyde, acrolein or the like by a conventional method in the presence of a base. The solvent may be THF, dimethoxyethane, or the like, and the base may be butyllithium (hexane solution), methyllithium, or the like.
And react for 1 hour. The obtained (13) preferably protects a hydroxyl group, and as the protecting group, the protecting groups described in (d) can be suitably used. The protecting group may be introduced by the method described above, and the protected form (14) is obtained in high yield.
Can be obtained.

(R) Compound (15) Compound (1) was obtained from compound (10) and compound (14).
5) can be synthesized. Compound (14) is treated with a base such as butyllithium (hexane solution), Grignard reagent, sodium hydride, or potassium amide in a solvent such as THF or dimethoxyethane to form metal acetylide. It may be dissolved in a solvent such as THF and added. The reaction is preferably carried out at -20 ° C to 0 ° C,
The reaction is carried out for about 3 hours to obtain an adduct (15) in which the epoxy is opened.

(Ii) Protecting group ((15) → (1)) To remove the protecting group, the method described in (f) can be used. The desired dihydropanaxacol can be obtained by deprotection.

(Effect of the Invention) According to the novel synthesis method of the present invention, it has become possible to synthesize a large amount of dihydropanaxacol and its related compounds, which were conventionally obtained only in very small amounts by extraction.

 Next, the present invention will be described with reference to examples.

(Example) Example 1 ((1) → (2)) L-(+)-tartaric acid diethyl ester (1) was mixed with 11.0 g of acetone dimethyl acetal (2,2-dimethoxypropan).
e) After dissolving in 50ml, camphorsulfonic acid (CSA) 100mg
And stirred in a 50-70 ° C. oil bath overnight. After cooling, 100 ml of ethyl acetate was added, and the mixture was poured into 50 ml of a 5% NaHCO ₃ solution to separate an organic layer. The aqueous layer was extracted with ethyl acetate, combined with the organic layer, washed twice with 80 ml of saturated saline, dried over Na ₂ SO ₄ and concentrated. The mixture obtained here was separated by silica gel column chromatography (hexane: ethyl acetate = 3: 1),
(2) (9.0 g, yield 68.5%) was obtained and 15% of the raw material was recovered.

Example 2 ((2) → (3)) 6.0 g of LiAl ₄ was added to 100 ml of anhydrous ether with stirring to form a suspension, and then an ether solution (40 ml) of compound (2) (7.7 g) was slowly added. The mixture was added dropwise and stirred at room temperature overnight.
Next, 20 ml of ethyl acetate was added dropwise, and the mixture was stirred for 30 minutes. Then, 30 ml of a saturated Rochelle salt solution was added, and the mixture was filtered and concentrated using celite as a filter aid. Compound (3) (3.7 g, yield: 77.%) was obtained from the obtained oily substance by silica gel column chromatography (hexane: ethyl acetate = 3: 1 and 1: 2). The obtained (3) was identical in NMR spectrum to the compound reported in K. Mori and S. Tanada (Tetrahedron 35: 1279-1284, 1979).

Example 3 ((3) → (4)) Paratoluenesulfonyl chloride (p-TsCl 3.0 g) was added to a pyridine solution (30 ml) of compound (3) (3.2 g), and the mixture was allowed to stand at room temperature overnight. Then, 100 ml of saturated saline was added, extracted with ethyl acetate, and concentrated under reduced pressure to obtain an oily substance. This oily substance was subjected to silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give compound (4) (3.4 g,
A yield of 54.5%) was obtained and 10% of the raw material was recovered. ^{1 H-NMR 1.35 (s)} (ppm) 1.38 (s) 2.20 (br, s) 2.45 (s) 3.74 (m) 4.15 (m) 7.35 (d, J = 8.3Hz) 7.77 (dJ = 8.3Hz) carried Example 4 ((4) → (5)) Compound (4) (1.7 g) in dichloromethane solution (10 ml)
To the mixture were added 3,4-cyhydro-2H-pyran (DHP, 670 mg, 1.5 equivalents) and 50 mg of CSA, and the mixture was stirred at room temperature for 30 minutes. After the reaction was completed, 50 ml of ethyl acetate was added, and the mixture was poured into saturated NaHCO ₃ water and extracted with ethyl acetate. Next, the organic layer was washed twice with a saturated saline solution (50 ml × 2), dried over Na ₂ SO ₄ , and concentrated. The obtained oil was subjected to silica gel column chromatography (hexane: ethyl acetate = 3: 1). And compound (5) (2.0 g,
Yield 93.0%). ^{1 H-NMR 1.35 (s)} (ppm) 1.38 (s) 1.57 (br, s) 2.45 (s) 3.52 (br, m) 3.57 (br, m) 4.14 (m) 4.61 (br, s) 7.34 (d , J = 8.3 Hz) 7.81 (d, J = 8.3 Hz) Example 5 ((5) → (6)) Cuprous iodide ¹⁾ (1.34 g, 3.0 eq) was converted to anhydrous ether (25
ml) and cooled to -40 ° C. Then, n-hexyllithium-ether ²⁾ (4.5 ml, 1.56 mmol / ml) was added dropwise and stirred for 15 minutes (at this time, the color of the reaction solution was pale yellow, but gradually changed from brown to black brown). became). Furthermore, n
-Hexyllithium / ether ²⁾ 4.5 ml (1.56 mmol / ml)
Was added dropwise and stirred for 15 minutes (the color of the reaction solution changed from black-brown to pale purple to dark blue-violet). Next, an ether solution (8 ml) of the compound (5) (930 mg) was added at a bath temperature of −30 ° C.
It was dropped in 10 minutes. (The color of the reaction solution changed from dark blue-purple to black as the solution was dropped). Further, after stirring at this temperature for 1 hour, a saturated ammonium chloride solution (10 m
l) was added and stirred for 20 minutes. Then, the mixture was extracted with ether, washed twice with a saturated saline solution (30 ml), dried over Na ₂ SO ₄ and concentrated. The obtained crude product was roughly fractionated by silica gel column chromatography (hexane: ether acetate = 7: 1), and then subjected to HPLC (Nucleosil 50-5,8 × 300 mm, hexane: ethyl acetate = 20: 1, 3.0 ml / ml). min) to give Compound (6) (500 mg, yield 66.4%, eluted at 17 minutes).

1) Commercially available cuprous iodide was washed with THF using a Soxhlet extractor and dried with a vacuum pump for 4-5 hours.

2) 11.8g lithium metal (30%) dispersion,
2.5 eq.) In anhydrous ether (60 ml) and stirred. n-bromohexane (3 ml, about 1/3 of the total amount used)
And stir at room temperature, and when the internal temperature rises,
Cooled to -15 ° C. Then, after the remaining n-bromohexane (25 ml) was gradually added, the mixture was further stirred at -15 ° C for 3-4 hours. The obtained hexyllithium solution was allowed to stand in a refrigerator, and the titer of the supernatant ether layer was assayed with sec-butanol (indicator: 1,10-phenanthrilone), and then used for the reaction.

Rf (hexane: ethyl acetate = 7: 1, silica gel thin layer chromatography, Art.5715, manufactured by Merck Ltd., 0.25 mm, the same in the following examples) = 0.33 Example 6 ((6) → (7)) Compound (6) ) (400mg) in methanol solution (4ml)
-HCl (1 ml) was added and the mixture was stirred at room temperature for 1 hour. Then, after adding 40 ml of ethyl acetate and washing twice with a saturated saline solution (10 Lm),
After drying and concentration over Na ₂ SO ₄ , compound (7) (206 mg, yield 8)
8.0%) as colorless crystals. ¹ H-NMR 0.95 (t, J = 7.1 Hz) (ppm) 1.2 to 1.4 (br, m) 1.50 (m) 3.62 (m) 3.75 (m) ¹³ C-NMR 14.1, 22.7, 25.8, 29.4 (ppm) 29.8, 31.9, 33.6, 64.5 72.4, 74.3, mp 48 ° C IR (CHCl ₃ ) cm ^-1 ; 3400 (m), 2925 (s), 2850 (m) Example 7 ((1) → (8)) Compound (7) Paratoluenesulfonyl chloride (p-TsCl) (185 mg) was added to a pyridine solution (2 ml) of (190 mg).
And left at room temperature overnight. Saturated saline (30 ml) was added, extracted with ethyl acetate, and the organic layer was dried over Na ₂ SO ₄ ,
Concentrated. The obtained mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 3: 1) to give compound (8) (150 m
g, yield 43.6%) as colorless crystals. ^{1 H-NMR 0.88 (t,} J = 7.3Hz) (ppm) 1.2~1.4 (br, m) 2.46 (s) 3.72 (br, m) 4.09 (d, J = 5.4Hz) 7.35 (d, J = 8.1 Hz) 7.80 (d, J = 8.1 Hz) mp 63 ° C IR (cm ^-1 ); 3550 (m), 2925 (s), 2850 (m), 1730 (m), 1600 (m), 1460 (m) Example 8 ((8) → (9)) To a solution of compound (8) (114 mg) in methanol (3.5 ml) was added anhydrous potassium carbonate (457 mg, 10 equivalents).
Stirred for hours. A saturated saline solution (40 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over Na ₂ SO ₄ and concentrated. The obtained mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 2: 1) to obtain compound (9) (55 mg, yield: 75.5%). ^{1 H-NMR 0.88 (t,} J = 7.3Hz) (ppm) 1.2~1.4 (br, m) 1.60 (m) 1.78 (d, J = 5.9Hz-CH) 2.72 (dd, J = 2.7,4.9Hz) 2.83 (t, J = 4.9 Hz) 2.98 (m) 3.44 (m) IR (cm ^-1 ); 3600 (w), 3500 (w), 3430 (s), 3360 (m) Example 9 ((9)) → (10)) Compound (9) (50 mg) in dichloromethane (1.5 m
DHP (40μ) and a trace amount of CSA were added to l), and the mixture was stirred at room temperature for 30 minutes. Next, a NaHCO ₃ solution (20 ml) was added to the reaction solution,
Extracted with ethyl acetate. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated. The obtained mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 3: 1) to obtain a compound (10) (67 mg, yield 90.0%).

Rf (hexane: ethyl acetate = 5: 1) = 0.40, 0.47 (mixture of diastereomers) ¹ H-NMR 0.88 (t, J = 7.3 Hz) (ppm) 1.2 to 1.4 (br, m) 1.5 to 1.7 (br , m) 1.76 (m) 1.84 (m) 2.49 (dd, J = 2.7, 4.9 Hz) 2.67 (dd, J = 2.7, 4.9 Hz) 2.76 (t, J = 4.9 Hz) 2.80 (t, J = 4.9 Hz) 2.95 (m) 3.09 (m) 3.38 (m) 3.50 (m) 3.88 (m) 4.00 (m) 4.70 (t, J = 4.4 Hz) 4.98 (t, J = 4.4 Hz) Example 10 ((11)) + (12) → (13) → (14)) THF solution of diacetylene (12) (15ml) (1mmol / ml)
Was cooled to −50 ° C. and stirred. To this, butyllithium-hexane (10 ml, 1.5 mmol / ml) and propionaldehyde ((11), 840 mg, 14.5 mmol) were gradually added dropwise, followed by another 30 minutes.
For a minute. Then, saturated ammonium chloride solution (50m
l) was added and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over Na ₂ SO ₄ and concentrated. The mixture obtained here is subjected to silica gel chromatography (hexane: ethyl acetate =
After separation and purification in 5: 1), the residue was dissolved in dichloromethane (10 ml), DHP (1 ml) and CSA (20 mg) were added, and the mixture was stirred at room temperature for 1 hour. A NaHCO ₃ solution (20 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, and then washed with Na ₂ S
Dried over O ₄ and concentrated. The obtained mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 7: 1) to obtain compound (14) (1.4 g, yield 50.0%).

Rf (hexane: ethyl acetate = 5: 1) = 0.60, 0.68 (mixture of diastereomers) ¹ H-NMR 1.00 (t, J = 7.3 Hz) (ppm) 1.04 (t, J = 7.3 Hz) 1.56 (m) 1.78 (m) 2.14 (d, J = 0.9 Hz) 2.15 (d, J = 0.9 Hz) 3.54 (m) 3.80 (m) 4.00 (m) 4.25 (t, J = 6.4 Hz) 4.41 (t, J = 6.4) Hz) 4.74 (t, J = 3.4 Hz) 4.93 (t, J = 3.4 Hz) Example 11 ((10) + (14) → (15)) A THF solution of compound (14) (77 mg, 0.4 mmol) ( 130μ
) Was cooled to -30 ° C, and butyllithium-hexane (23
0μ, 0.3mmol) and HMPA (50μ, 0.3mmol) were slowly added dropwise. Then, T of compound (10) (25 mg, 0.1 mmol)
An HF solution (100 μ) was added dropwise, and the mixture was stirred at −30 ° C. for 2 hours. After the completion of the reaction, a saturated NH ₄ Cl solution (10 ml) was added, and the mixture was extracted with ethyl acetate. After washing the organic layer with saturated saline, Na ₂ S
Dried over O ₄ and concentrated. The resulting mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 5: 1) to give the compound (1
5) (20 mg, 44.4% yield) was obtained.

Rf (hexane: ethyl acetate = 5: 1) = 0.22, 0.26 (mixture of diastereomers) Example 12 ((15) → (1)) Compound (15) (10 mg) in methanol (500 μ)
A small amount of CSA was added to the mixture and stirred at room temperature for 1 hour. Then
After adding ethyl acetate (10 ml) and washing with saturated saline, Na ₂ S
Dried over O ₄ and concentrated. This was analyzed by HPLC (Nucleosil 50-5,8
× 300mm, hexane: EtOAc = 2: 1, 3.0ml / min) to separate and purify the compound (1) (4mg, 64.5% yield, eluted in 22 minutes)
I got ¹ H-NMR 0.89 (t, J = 7.1 Hz) (ppm) 1.01 (t, J = 7.3 Hz) 1.2 to 1.4 (br, m) 1.50 (m) 1.74 (m) 2.57 (dd, J = 6.4, 16.9) Hz) 2.59 (dd, J = 5.6, 16.9 Hz) 3.58 (m) 3.63 (m) 4.35 (t, J = 6.4 Hz) IR (CHCl ₃ ) cm ^-1 ; 3600 (w), 2930 (s) 2860 ( m), 2260 (w) 〔[α] ^{20 ゜} _D ▼ = -17.0 The compound (1) obtained in this example was compared with dihydropanaxacol obtained by reducing panaxacol obtained from nature. . The following method was used for the reduction of panaxacol.

Panakisakoru a (74 mg) was dissolved in methanol (1.0 ml), was added an excess of NaBH ₄ under stirring. After about 30 minutes,
Saturated saline (10 ml) was added, and the mixture was extracted with ethyl acetate.
The extract was dried over Na ₂ SO ₄ and after concentration, the resulting oil was removed.
Purified by HPLC (Nucleosil 50-5, 8 × 300 mm, hexane: ethyl acetate = 1: 1), dihydropanaxacol (60 m
g, yield 80.0%).

The NMR spectra of the obtained dihydropanaxacol and the compound (1) synthesized by the method of the present invention were measured and compared. Compound (1) was confirmed to be dihydropanaxacol.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Keiichi Ushiyama 1-1-2 Shimohozumi, Ibaraki-shi, Osaka Nitto Denko Corporation

Claims (1)

(57) [Claims] 1. Compound (A) (Wherein R ¹ represents ^one of a tetrahydropyranyl group and a trialkylsilyl group) and the compound (B) (Wherein R ² represents any one of a tetrahydropyranyl group and a trialkylsilyl group, and R ³ represents an ethyl group.) In the presence of a base to give a compound (C) (Wherein R ¹ and R ² each represent either a tetrahydropyranyl group or a trialkylsilyl group, and R ³ represents an ethyl group.). ) (Wherein, R ³ represents an ethyl group.)