JP2000086647A - Both enantiomers of cis-3-methyl-4-decanolide and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a production method for obtaining both enantiomers of cis-3-methyl-4-decanolide with high optical purity. SOLUTION: From both enantiomers of 2-oxabicyclo [3.3.0] oct-6-en-3-one, 2-alkoxy-4-tosiloxymethyl-5- (2'-tosiloxyethyl) tetrahydrofuran The two enantiomers of 2-alkoxy-4-tosyloxymethyl-5-n-hexyltetrahydrofuran obtained by selective alkylation are reduced and then oxidized to give cis-3-methyl-4.
-To provide a process for obtaining both enantiomers of decanolide with high optical purity.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel enantiomer of cis-3-methyl-4-decanolide, which is useful as a perfume raw material for a perfuming composition such as cosmetics, food and drink, a method for producing the same, and a method for producing the same. The present invention relates to a fragrance composition containing the same.

[0002]

BACKGROUND OF THE INVENTION Cis-3-methyl-4-decanolide is
Nocturnal orchids native to the Kenyan region of Africa; Roman Kaiser (R. Kaiser) from natural products as an aroma component of Erangis kirkii
Is a compound having a ripe fruit and wine-like aroma, which is disclosed for the first time by a radical addition reaction of methyl crotonate and heptanol. R. Kais
er.The Scent of Orchids: Olfactory and Chemical Inv
estigations, Elesevier, Amsterdam, 1993).

[0003]

However, in the above synthesis method, only racemic cis-3-methyl-4-decanolide containing a racemic-trans form can be obtained, which is extremely useful in the perfumery industry. There is no hope to obtain optically active cis-3-methyl-4-decanolide. Furthermore, since the aroma differs greatly between the optical isomers, it was necessary to synthesize a mirror image and determine the aroma in order to identify it as a substance exhibiting the characteristics of the aroma of Erangis kirkii. .

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, a commercially available raw material of prostaglandin, (1R, 5S) -2-oxabicyclo [3. 3.0] oct-6-en-3-one (compound of formula 2) or (1S, 5R) -2-oxabicyclo [3.3.0] oct-6-en-3-one (formula 2) 'Compound),

[0005]

Embedded image Is used as a starting material, a novel compound represented by the formula (1), which is both enantiomers of cis-3-methyl-4-decanolide,
4R) -cis-3-methyl-4-decanolide or (3S, 4S) -cis-3-methyl-4-decanolide represented by the formula (1 ′)

[0006]

Embedded image Of the present invention with high optical purity, and completed the present invention.

[0007] Accordingly, an object of the present invention is to provide an enantiomer, cis-3-, which is different from racemic cis-3-methyl-4-decanolide, which is found as an aroma component of Erangis kirkii. Methyl-4-decanolide is synthesized, the absolute configuration of the enantiomer is determined, and the fragrance of these enantiomers is determined. As a fragrance useful in the fragrance industry, various cosmetics, foods and drinks, etc. An object of the present invention is to provide a perfume composition that can be blended.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The compound of formula (1) of the present invention
R, 5S) -2-oxabicyclo [3.3.0] oct-6-en-3-one can be synthesized by using, for example, the following reaction steps as a starting material. In addition,
In the case of the compound of formula (1 ′), it can be synthesized in exactly the same manner using (1S, 5R) -2-oxabicyclo [3.3.0] oct-6-en-3-one as a starting material.
The odor of the obtained (3R, 4R) -cis-3-methyl-4-decanolide (compound of the formula 1) has a lactone smell with an oily smell in the top note, and the middle note has an exciting odor with the lactone smell. It is a persistent fragrance with a green feeling (blue smell).

The aroma of (3S, 4S) -cis-3-methyl-4-decanolide (compound of the formula 1 ') is such that the top note is a ripe fruity aroma with a strong intensity, and the middle note is a waxy aroma. It has a long lasting fragrance with a milky aroma.

[0010]

Embedded image

The starting material (1R, 5S) -2-oxabicyclo [3.3.0] oct-6-en-3-one or (1S, 5R)-as a starting material that can be used in the present invention.
2-oxabicyclo [3.3.0] oct-6-ene-
It is desirable that the 3-one has as high an optical purity as possible.

The reducing agent used for obtaining the compound of the formula (3) in the above reaction step includes, for example, diisobutylaluminum hydride. As alcohols represented by —CH ₂ OH, R is hydrogen or C ₁ -C ₁₀
And methyl alcohol, ethyl alcohol, propyl alcohol, butyl alcohol, pentyl alcohol, hexyl alcohol, heptyl alcohol and the like.

The oxidative cleavage agent used to obtain the compound of the formula (4) in the above reaction step can be exemplified by osmium tetroxide and sodium periodate. For example, a reducing agent such as sodium borohydride can be used.

After tosyl chloride is added to the compound of the formula (4) and tosyl chloride is added, the resulting compound of the formula (5) is selectively alkylated by adding copper iodide and lithium n-butyryl to obtain a compound of the formula (5) The compound of 6) can be obtained.

Next, the compound of the formula (6) is subjected to a reduction reaction to obtain a compound of the formula (7). As a reducing agent which can be used in this case, for example, lithium triethylborohydride is exemplified. it can. Finally, the compound of formula (7) is subjected to a hydrolytic oxidation reaction to give the cis-33-
It can be obtained as both enantiomers of methyl-4-decanolide, and this reaction is to react the compound of the formula (7) with aqueous hydrogen peroxide under hydrochloric acid.

[0016]

The present invention will be described in more detail with reference to the following examples.

Example 1 Synthesis of (1R, 3S, 5S) -3-n-hexyloxy-2-oxabicyclo [3.3.0] oct-6-ene (compound of formula 3) ) -2-oxabicyclo [3.
3.0] Oct-6-en-3-one (compound of formula 2)
(2.6 g, 20.9 mmol) in a dry toluene solution (110 ml) was slowly added dropwise with a toluene solution of diisobutylaluminum hydride (1.01 M, 22.8 ml) at −78 ° C. while purging with argon. After the reaction solution was further dropped and stirred for about 1 hour, methanol (20 m
l) was added slowly. The temperature was further raised to room temperature, a saturated aqueous solution of Rochelle salt was added, and the mixture was stirred for 1 hour. The solution was extracted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated by filtration to give a colorless oil. This was stirred overnight at room temperature with 1-hexanol (11 ml) and a catalytic amount of p-toluenesulfonic acid in methylene chloride (10 ml). The reaction solution was stirred for a while after adding a small amount of sodium hydrogen carbonate, concentrated, and then separated into two diastereomers by silica gel chromatography. (Compound of formula 3) (3.11 g, 72
%) And the following (compounds of formula 3-1 (1R, 3R, 5
S) form) (0.492 g, 14%).

[0018]

Embedded image

Low polar diastereomer (compound of formula 3)
Analytical value for n _D ^23.1 = 1.4601. [Α] _D ²⁴ = + 114 (c = 0.98, MeOH). IR
ν _max (film) cm ^-1 : 3054 (m), 1617 (w), 1444 (m), 11
87 (m). ¹ H-NMR (300 MHz, CDCl ₃ ) δ: 0.89 (3H, t, J =
6.7), 1.26 to 1.61 (8H, m), 1.80 (1H, ddd, J = 5.1, 5.1,
13), 2.12 (1H, ddd, J = 1.2, 9.5, 13), 2.41 to 2.63 (2
H, m), 3.32 to 3.40 (2H, m), 3.66 (1H, dt, J = 6.9, 9.5),
4.72 (1H, t, J = 6.1), 5.10 (1H, d, J = 5.4), 5.59 (2H,
m) (Found: C, 74.14; H, 10.55.Calc for C ₁₃ H ₂₂ O ₂ :
(C, 74.24; H, 10.54.)

Analytical value of highly polar diastereomer (compound (1R, 3R, 5S) of formula 3-1) n _D ^23.8 = 1.4599 [α] _D ^18.5 = -41.8 (c = 1.02, MeO
H) .IR ν _max (film) cm ^-1 : 3057 (m), 1620 (w), 1466
. (m), 1161 (s ) 1 H-NMR (300MHz, CDCl 3) δ: 0.88 (3H,
t), 1.23 to 1.58 (8H, m), 1.92 (1H, d, J = 21), 2.09 (1
H, m), 2.47 to 2.69 (2H, m), 3.26 to 3.35 (2H, m), 3.56
(1H, dt, J = 7.1, 9.4), 4.83 (1H, t, J = 6.6), 5.09 (1H,
t, J = 5.3), 5.58 to 5.67 (2H, m) (Found: C, 74.08; H,
10.51.Calc for C ₁₃ H ₂₂ O ₂ : C, 74.24; H, 10.54.)

In exactly the same manner as above, (1S, 5R)-
2-oxabicyclo [3.3.0] oct-6-ene-
(1S, 3) obtained from 3-one (compound of formula 2 ′)
R, 5R) -3-n-hexyloxy-2-oxabicyclo [3.3.0] oct-6-ene (compound of formula 3 ')
Was consistent with the data for the compound of Formula 3.

Example 2 Synthesis of (2R, 3S, 5S) -2-n-hexyloxy-4-hydroxymethyl-5- (2′-hydroxyethyl) tetrahydrofuran (compound of formula 4) (compound of formula 3) 4.16 g (1.98 mmol) of osmium tetroxide in a mixed solvent of ether and water (320 ml, 1: 1) (38 ml,
0.039M) and sodium periodate (12.7 g,
5.94 mmol) and stirred at room temperature for 3 hours. Thereafter, the mixture was extracted with ethyl acetate, washed with hypo and brine, dried over magnesium sulfate and concentrated. This was purified without further purification using sodium borohydride (3.75 g, 9.91
mmol) in a mixed solvent of THF and water (160 ml, 1:
1) A solution of THF (60 ml) was added dropwise at -10 ° C. The reaction mixture was stirred for 1 hour, neutralized with 1M hydrochloric acid, extracted with ethyl acetate, washed with brine, dried over magnesium sulfate, concentrated and chromatographed to give a colorless oil (formula 4) Compound) was obtained.
(2.78 g, 57%)

Analytical value of the compound of formula 4 n _D ^23.1 = 1.4681. [Α] _D ²⁴ = + 97.9 (c = 0.98, MeOH). IR
ν _max (film) cm ^-1 : 3377 (s), 2931 (s), 1455 (m), 1
340 (m). ¹ H-NMR (300 MHz, CDCl ₃ ) δ: 0.89 (3H, t),
1.21 to 1.39 (6H, m), 1.43 to 1.62 (2H, dt, J = 6.8, 14)
1.74 to 2.15 (4H, m), 2.51 (1H, m), 3.36 (1H, dt, J = 6.7,
9.6), 3.54 to 3.88 (5H, m), 4.27 (1H, m), 5.11 (1H, dd,
J = 2.3, 5.3), HR-FABMS calcd for 247.1808, found
247,1884

The compound of formula 4 'similarly obtained from the compound of formula 3'
The analytical value of the compound was n _D ^19.3 = 1.4680. [Α] _D ²⁴ = -101
(c = 1.04, MeOH), and its IR and ¹ H-NMR spectra were consistent with the data for the compound of formula 4. HR-FABMS calcd for 2
47.1808, found 247,1884

Example 3 Synthesis of (2R, 3S, 5S) -2-n-hexyloxy-4-tosyloxymethyl-5- (2'-tosyloxyethyl) tetrahydrofuran (compound of formula 5) Compound of formula 4 DMAP (9 mg, cat.) In a pyridine solution (4 ml) of 0.364 g (1.48 mmol).
, Tosyl chloride (1.13 g, 5.93 m)
mol) at −10 ° C., and the mixture was stirred for 4 hours under argon substitution. The reaction solution was added with water (0.1 ml), diluted with ether, and washed with cold hydrochloric acid, water, saturated aqueous sodium bicarbonate, and brine.
After drying over magnesium sulfate and concentration, it was purified by chromatography. (0.725 g, crude yield 88%)
The compound of formula 5 was used in the next reaction without further purification.

[0026] Analysis for the formula value of 5 compounds ^{_{IR ν max (film) cm -1}} :. 2931, 1360, 1097, 1096) 1
H-NMR (300 MHz, CDCl ₃ ) δ: 0.88 (3H, t, J = 6.9), 1.27
(6H, m), 1.46 to 1.95 (6H, m), 2.46 (6H, s) 2.59 (1H, m),
3.26 (1H, dt, J = 6.0, 9.6), 3.52 (1H, dt, J = 7.2, 9.
6), 3.83 (1H, dd, J = 6.6, 9.7), 3.93 (1H, dd, J = 7.6,
9.7), 4.06 to 4.15 (3H, m), 4.95 (1H, dd, J = 1.7,5.3),
7.33 to 7.37 (4H, dd, J = 3.3, 8.3), 7.75 to 7.79 (4H, dd,
J = 6.1,8.2).

The compound of formula 5 ′ similarly obtained from the compound of formula 4 ′
The IR and ¹ H-NMR spectra of the compound of the formula ¹ were consistent with the analytical values of the compound of the formula 5.

Example 4 Synthesis of (2R, 3S, 5S) -2-n-hexyloxy-4-tosyloxymethyl-5-n-hexyltetrahydrofuran (compound of formula 6) Dry monovalent copper iodide (0 .299g, 1.6mmo
l) A solution of n-butyllithium in hexane (2 ml, 1.56 M) was slowly added to an ether solution (30 ml) of
It is added dropwise at 0 ° C. while replacing with argon. After stirring for 1.5 hours, the ditosylate (compound of formula 5) (0.725 g, 1.3
An ether solution (1 mmol) (15 ml) was added dropwise at -40 ° C, and the mixture was stirred for 2.5 hours. The reaction solution was poured into an ice-cooled saturated ammonium chloride solution, extracted with ether, washed with ammonium chloride and brine, dried over magnesium sulfate, concentrated and chromatographed. Thus, the starting material, monotosylate (compound of formula 6) and by-products shown below (compound of formula 6-1) were separated.
The compound of formula 6 was used in the next reaction without further purification.

[0029]

Embedded image

Analytical value of compound of formula 6 IR ν _max (film) cm ⁻¹ : 1188, 1177, 1097 (m), 1032.
¹ H-NMR (300MHz, CDCl ₃ ) δ: 0.88 (3H, t, J = 7.0), 1.
21 to 1,55 (18H, m), 1.84 to 1.98 (2H, m), 2.45 (3H, s)
2.54 (1H, m), 3.33 (1H, dt, J = 6.6, 9.7), 3.60 (1H, d
t, J = 6.7, 9.6), 3.78 (1H, dd, J = 8.2,), 3.98 to 4.07
(2H, m), 4.98 (1H, dd, J = 2.5, 5.4), 7.33 to 7.36 (2H,
d, J = 8.2), 7.77 to 7.80 (2H, d, J = 8.3)

The compound of formula 6 ′ similarly obtained from the compound of formula 5 ′
The analytical value of the compound of the formula 1 was consistent with the analytical value of the compound of the formula 6.

Example 5 Synthesis of (2R, 3S, 5S) -2-n-hexyloxy-4-methyl-5-n-hexyltetrahydrofuran (compound of formula 7) Compound of formula 6 (0.198 g, 0.45 mmol) ) T
A hexane solution (1.35 ml, 1M) of lithium triethylborohydride was added dropwise to the HF solution (2 ml) at -10 ° C under an argon stream. The reaction solution is stirred at room temperature for 16 hours, poured into water and extracted with hexane. The extract was washed with brine, dried over magnesium sulfate, concentrated, purified by chromatography and distillation to give the compound of formula 7.
(0.097 g, 80%, 3 steps 24%)

Analytical value of the compound of the formula 7 n _D ^19.2 = 1.4429. [Α] _D ^18.8 = + 74,5 (c = 1.04, MeOH) .IR
^{_{ν max (film) cm -1:}} 2933, 2858, 1100, 1064. 1 H-NMR
(300MHz, CDCl ₃ ) δ: 0.85-0.90 (3H, m), 1.24-1,58
(18H, m), 1.76 (1H, ddd, J = 4.1, 5.7, 13.3), 2.00 (1
H, ddd, J = 2.9, 7.5, 13.3) 2.28 (1H, m), 3.37 (1H, dt,
J = 6.6, 13.5), 3.68 (1H, dt, J = 5.2, 13.6), 3.97 (1
(H, m), 5.09 (1H, dd, J = 2.9, 5.7). (Found: C, 75.19;
H, 12.60 Calcd. For C ₁₇ H ₃₄ O ₂ : C, 75.50; H, 12.67)

Similarly, the analytical value of the compound of the formula 6 '(compound of the formula 7') is n _D ^25.8 = 1.4413. [Α] _D
^20.6 = -76.1 (c = 1.03, MeOH), and IR and ¹ H-NMR
The spectrum was consistent with the analytical value of (compound of formula 7).
(Found: C, 75.48; H, 12.59 Calcd. For C ₁₇ H ₃₄ O ₂ :
(C, 75.50; H, 12.67)

Example 6 Synthesis of (3R, 4R) -cis-3-methyl-4-decanolide (compound of formula 1) Compound of formula 7 (0.097 g,
Hydrogen peroxide (34%, 0.11 ml) and 12 N hydrochloric acid (0.05 ml) were added dropwise to a methanol solution (1 ml) of 0.36 mmol) at -10 ° C. The reaction solution was -1
After stirring at 0 ° C for 30 minutes, the mixture was heated to 40 ° C and stirred for 3 hours. The reaction solution was diluted with water, extracted with ethyl acetate, washed with hypo and brine, dried over magnesium sulfate and concentrated, and then subjected to silica gel chromatography (formula 1).
Was obtained. (0.058g, 88%)

Analytical value of compound of formula 1 ¹ H-NMR (300 MHz, CDCl ₃ ) δ: 0.87 (3H, t, J = 6.4), 0.99
(3H, d, J = 6.9), 1.27 to 1,71 (10H, m), 2.16 (1H, dd, J
= 3.6, 16.6), 2.51 to 2.61 (1H, m), 2.67 (1H, dd, J = 7.7,
16.7), 4.42 (1H, m). N _D ^18.8 = 1.4522. [Α] _D ^21.9 = 5
9.7500 (c = 0.40, CHCl ₃ ) .IR ν _max (film) cm ^-1 : 2957
(s), 1779 (s), 1171 (m) (Found: C, 71.42; H, 10.7
_{. 8 Calcd for C 11 H 20} O 2: C, 71.70; H, 10.94)

Similarly, the analytical value of the compound of formula 1 ′ obtained from the compound of formula 7 ′ is n _D ^24.1 = 1.4496. [Α] _D ^23.0
= -57.6113 (c = 1.06, CHCl ₃ ). (Found: C, 71.70; H, 10.
86 Calcd. For C ₁₁ H ₂₀ O ₂ : C, 71.70; H, 10.94).

As described above, both enantiomers of cis-3-methyl-4-decanolide are compounds having a very distinctive odor, and are expected to be used in the future for flavoring cosmetics, foods and drinks, etc. It can be said that it is a substance.

Examples 7 to 8 The following components (parts by weight) were prepared as a orchid-type compounded flavor composition.
Was mixed.

The compound of the formula 1 (3
R, 4R) -cis-3-methyl-4-decanolide 90 g
The addition of (Example 7) resulted in a new formulated perfume composition having a fresher and more natural orchid type with an enhanced persistence. Also, by adding a compound of formula 1 'in place of the compound of formula 1 above (Example 8), a new compounded perfume composition having a natural orchid type with a slightly sweet and ripe feel with enhanced persistence Thing was obtained.

[0041]

According to the present invention, both enantiomers of cis-3-methyl-4-decanolide, which could not be obtained by the conventionally known synthesis method, can be obtained with high purity, and both of these enantiomers have a very characteristic odor. Since it is a compound, it can be provided as a promising fragrance substance for flavoring in cosmetics, foods and drinks, etc. in the future.

Claims (3)

[Claims] 1. Formula (1) and formula (1 ′),
(3R, 4R) -cis-3-methyl-4-decanolide and (3S, 4S) -cis-3-methyl-4-decanolide. Embedded image 2. Formula (2) and Formula (2 ′) (1R, 5S) -2-oxabicyclo [3.
3.0] Oct-6-en-3-one (compound of formula 2)
Or (1S, 5R) -2-oxabicyclo [3.3.
0] Oct-6-en-3-one (compound of formula 2 ′) is subjected to a reduction reaction, and then, in the presence of an acid, a compound of the general formula R—CH ₂ OH
(Where R represents hydrogen or an alkyl group of C ₁ -C ₁₀ ) by an alkylation reaction to give a compound of formula (3) or (3 ′) (Where R represents hydrogen or a C ₁ -C ₁₀ alkyl group) (1R, 3S, 5S) -3-alkoxy-2-oxabicyclo [3.3.0] oct-6- Ene (compound of formula 3) or (1S, 3R, 5R) -3-alkoxy-2-oxabicyclo [3.3.0] oct-
6-ene (a compound of formula 3 ′) was prepared and obtained (formula 3
After oxidative cleavage of the compound of formula (3) or (compound of formula 3 ′), the compound is reduced to give a compound of formula (4) or (4 ′). (Wherein, R represents hydrogen or C ₁ -C ₁₀ alkyl radical are the,) represented by (2R, 3S, 5S)-2-alkoxy-4-hydroxy-5- (2'-hydroxyethyl) tetrahydrofuran (Compound of formula 4) or (2
(S, 3R, 5R) -2-Alkoxy-4-hydroxymethyl-5- (2′-hydroxyethyl) tetrahydrofuran (compound of formula 4 ′) was prepared and obtained (compound of formula 4) or (formula 4). Tosyl chloride by adding tosyl chloride to formula (5) or formula (5 ′). (Where R represents hydrogen or a C ₁ -C ₁₀ alkyl group) (2R, 3S, 5S) -2-alkoxy-4-tosiloxymethyl-5- (2′-tosiloxyethyl) ) Tetrahydrofuran (compound of formula 5) or (2)
(S, 3R, 5R) -2-Alkoxy-4-tosyloxymethyl-5- (2′-tosyloxyethyl) tetrahydrofuran (compound of formula 5 ′) was prepared and obtained (compound of formula 5) or ( Copper iodide and n-
By selective alkylation by adding and reacting butyllithium, the compound of formula (6) or (6 ′) (Where R represents hydrogen or a C ₁ -C ₁₀ alkyl group) (2R, 3S, 5S) -2-alkoxy-4-tosyloxymethyl-5-n-hexyltetrahydrofuran (Formula 6 Compound) or (2S, 3R, 5R)
-2-alkoxy-4-tosyloxymethyl-5-n-hexyltetrahydrofuran (compound of formula 6)
Next, the obtained (compound of formula 6) or (compound of formula 6 ′) is subjected to a reduction reaction to obtain a compound of formula (7) or formula (7 ′). (Wherein, R represents hydrogen or C ₁ -C ₁₀ alkyl radical are the,) represented by (2R, 3S, 5S)-2-alkoxy-4-methyl -5-n-hexyl-tetrahydrofuran (compound of formula 7 Or (2S, 3R, 5R) -2-alkoxy-4-methyl-5-n-hexyltetrahydrofuran (compound of formula 7 '), and finally hydrolyzing and oxidizing the compound of formula (1) Or the formula (1 ′) Preparation of (3R, 4R) -cis-3-methyl-4-decanolide (compound of formula 1) or (3S, 4S) -cis-3-methyl-4-decanolide (compound of formula 1 ′) Method. 3. (3R, 4R) -cis-3-methyl-4
-Decanolide and / or (3S, 4S) -cis-3
A fragrance composition comprising -methyl-4-decanolide.