JPS62209072A - Production of optically active alpha-tocopherol - Google Patents

Abstract

PURPOSE:To obtain the titled compound without requiring optical resolution of the dl-isomer, by using a 2,3-epoxy derivative obtained by enantioselective oxidation of natural phytol as a starting raw material. CONSTITUTION:A compound expressed by formula I (R1 is formula II) is reacted with p-toluenesulfonyl chloride to give a compound expressed by formula III (Ts is tosyl), which is then reacted with isopropyl mercaptan in the presence of metallic sodium to afford a compound expressed by formula IV. The resultant compound expressed by formula IV is further reductively cleaved to provide a compound expressed by formula V, which is then acetylated and reacted with 4-acetoxy-2,3,5-trimethylphenol to give a compound expressed by formula VI. The resultant compound expressed by formula VI is reacted with Raney nickel and further deacetylated to afford a compound expressed by formula VII, which is then directly cyclized to provide a compound expressed by formula VIII. The compound expressed by formula VII is oxidized and cyclized to give a compound expressed by formula IX. Furthermore, the compound expressed by formula X is used as a starting raw material to give an intermediate expressed by formula XI.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel method for producing industrially useful optically active α-tocopherol.

[Conventional technology and problems]

d-α-tocopherol is the most representative form of vitamin E that is widely distributed in nature.
It is widely used and is an extremely important substance among vitamin E.

However, d-α-tocopherol must be isolated from natural products, mainly vegetable oils, and is not suitable for industrial mass production. That is, since the content of d-α-tocopherol in vegetable oil is extremely small, an extremely large amount of vegetable oil is required, and separation and purification from homologues such as β, T, and δ are required, making isolation difficult. It also has the disadvantage of being difficult.

Therefore, various attempts have been made to chemically synthesize optically active α-tocopherol, especially d-α-tocopherol (for example, HoMayler, 0.15l
er et al., He1v, China, ^c ta +
46 +650 (1963); J, 'A, 5c
ott, W. M., Cort, H. Harley.

F, T, Bizzarro+ Ro, R, Pan1
sh, G, 5auey+ J, A.

C,S, 51.200 (1974), 52. 17
4 (1975); He1v.

Chim, Acta, 59. 290 (197
6); K., Chan, N.

Cohen et al., J. Org. Chem, 41
．． 3497.3512 (1976), prefecture, 3435
(1978), etc.), but the method is industrially useful.

That is, all of the conventionally proposed methods require the optical resolution of 41 intermediate substances at some point. The necessity of this optical resolution means that the yield is 3.
It has the major drawback of a significant reduction of 0 to 40%, and cannot be called an industrial method.

[Means for solving problems]

As a result of many years of research into a method that does not require optical resolution of di-isomers, the present inventors have discovered that this is possible by the method described below, and have now completed the present invention. Ta.

That is, the present invention represents the following structural formula: The same applies hereinafter] A compound represented by the following is tosylated with p-1-luenesulfonyl chloride to represent the structural formula: The same applies hereinafter] A compound represented by is obtained, and the compound is then reacted with isopropyl mercaptan in the presence of metallic sodium to obtain a compound represented by the structural formula: The compound is then reductively cleaved to form the structural formula: A compound represented by is obtained, and then the compound is acetylated to have the following structural formula: [wherein, Ac represents an acetyl group]. The same applies hereinafter] to obtain a compound represented by 4-acetoxy-2
, 3,5-1-limethylphenol to obtain a compound represented by the structural formula: The compound is then reacted with Raney nickel and further deacetylated to obtain a compound represented by the structural formula: The compound is directly cyclized or oxidized to obtain α-tocopherylquinone, which is then cyclized. The present invention provides a method for producing tocopherol or (2S, 4°R, 8″R)-α-tocopherol represented by the structural formula: Furthermore, the present invention reductively cleaves the compound represented by the above structural formula (I) to obtain a compound represented by the structural formula: Next, the compound is tosylated with p-toluenesulfonyl chloride. [the same applies hereinafter] A compound represented by υH is obtained, and then the compound is reacted with isopropyl mercaptan in the presence of metallic sodium to obtain a compound represented by the structural formula (IV) or (■゛). After obtaining, (V) or (■゛), (VI) in the same manner as above
The present invention also provides a method for obtaining optically active α-tocopherol (■) or (■'') through (■) or (■').

The synthesis route for α-tocopherol according to the method of the present invention is summarized below.

In addition, in the present invention, optically active α-tocopherol is
(2R,4”R,8”R)-α-tocopherol, (2
S, 4°R, 8°R)-α-tocopherol.

Synthetic route of α-tocopherol (1) (I') (IX)
(II) (n') (I
X') (X) (III) (I
II') (X') (IV)
(IV') (V)
(V') (VI)
(Vl') (■)
(■l) The present invention will be explained in more detail below.

The above structural formula (
The phytols represented by I) or (B) can be produced, for example, by the method disclosed in JP-A-57-136582.

For example, the case of natural phytol is specifically described below.

Enantioselective oxidation (enantioselective ox
idaLion) to obtain a 2,3-epoxy compound. To give an example of a specific method, dichloroethane,
A tartaric acid ester obtained by oxidizing natural phytol, tartaric acid diester, titanium triisopropoxide, and t-butybutyrobar oxide in a halogenated hydrocarbon such as tonochloroethane at a temperature of -70 to 30°C. For example, diethyl tartrate, dimethyl tartrate, etc. can be used, but in the case of diethyl tartrate, L
If -(+)-diethyl tartrate is used, the above structural formula (1)
Only the 2S,3S-epoxy compound having the steric structure represented by the above structure can be obtained, but if D-(-)-diethyl tartrate is used, only the 2R,3R-epoxy compound having the steric structure shown by the above structural formula (bi) can be obtained. is obtained.

The step from (1) or (B) to (IX) or (■'') is a step in which each 2,3-epoxy compound is reductively cleaved to obtain (IX) or (■'). Reduction. Good results can be obtained by using, for example, lithium aluminum hydride for the cleavage.In this case, an ether solvent such as diethyl ether or tetrahydrofuran is used as the solvent, and the temperature is not particularly limited, but usually about The reaction is carried out at -10°C to 40°C.

Steps from (I) or (■゛) to (n) or (■'), or from (IX) or (■゛) to (X) or (X゛)
The step leading to is the tosylation step. That is, (1) or (
■°), or (IX) or (■″) is reacted by adding p-)luenesulfonyl chloride in the presence of pyridine or the like.

Steps from (n) or (■') to (II[) or (■'), or from (X) or (X゛) to (IV) or (■
The step leading to step (°) is a step of adding isopropyl mercaptan in the presence of metallic sodium to obtain a sulfide.

The process from (I[I) or ku■°) to (rl/) or (■゛) is the same as the process of obtaining (IX) or (■'') from (I) or (bi) above. This is done by cleavage.

The step of obtaining (V) or (■°) from (IV) or (■゛) is an acetylation step, in which acetylation is performed using an acetylating agent such as acetic anhydride.

The step of obtaining (VI) or (■゛) from (V) or (■゛) is carried out by adding and reacting 4-acetoxy-2,3,5-trimethylphenol.

These (V), (V″), (Vl), and (■゛) are new compounds.

The step of obtaining (■) or (■') from (VI) or (■゛) is a step of deacetylation by reaction with Raney nickel. Deacetylation is carried out by reductively removing acetyl groups using lithium aluminum hydride or the like.

(■) or (■°) to optically active α, which is the final target substance
- The process of obtaining tocopherol (■) or (■゛) is (
■) or (■゛) is directly cyclized or oxidized using p-toluenesulfonic acid, anhydrous zinc chloride, etc. to obtain α-tocopherylquinone represented by the structural formula: For example, palladium/ This is carried out by cyclization using a carbon catalyst and p-toluenesulfonic acid or anhydrous zinc chloride.

Examples of the oxidizing agent used in the oxidation step include lead dioxide, silver oxide, hydrogen peroxide, Flemy's salt, etc., but in short, any oxidizing agent that can convert hydroquinone to quinone can be used. It is.

Obtained by the method of the present invention (2R, 4°R, 8'R)
It was confirmed from the physicochemical properties that -α-tocopherol is the same as naturally occurring d-α-tocopherol. - By way of example, the method of the invention j) results in (
2R,4'R,8'R)-α-tocopherol acetate and KJe(CN) & oxide, natural d-α
- When the optical rotation of tocopherol was compared with that of each corresponding substance, the two matched.

〔Effect of the invention〕

The method of the present invention does not require di-splitting and can industrially produce optically active α-tocopherol in high yield, and therefore the value of the present invention is extremely high.

〔Example〕

Examples are listed below, but it goes without saying that the present invention is not limited thereto.

Example 1 (2S, 3S, 7R, IIR) -2,3-epoxy-
Ao (2S,3S,7R,IIR)-2,3-epoxy-3 of 3,7,11,15-tetramethylhexadecyl tosylate
, 7,11,15-tetramethylhexadecane-1-ol (synthesized according to Example 1 of JP-A-57-136582) 5, OOg (16a + mol) was dissolved in pyridine 40-, and p- ) Add 6.10 g (32 mmol) of luenesulfonyl chloride as crystals,
After stirring for 90 minutes, it was stored in the refrigerator overnight. ice water 5
The reaction solution was poured into a container and extracted with ether. The extract was washed and dried, and the solvent was distilled off to obtain 5.84 g of the title compound (yield 93%).

The refractive index, IR spectrum, and NMR spectrum of the obtained compound are as follows.

n o” 1.4886 IR spectrum: 2930.1600.1500.13
70.1190°1180cm-' NMR7! , vector (CC14): δ0.82(1
211,d, J=611z).

1.13 (24Lbs), 2.36 (3H,s),
2.74 (111,t, J-611z).

3.94 (211, d, J=611z), 7.23
(2H), 7.64 (2H) (8 BQ.

J=811z) Example 2 (2R,3R,7R,11R)-2,3-epoxy-3
, 25.4 g (81,3-mol) of 7,11,15-tetramethylhexadecane-1-ol (synthesized according to Example 2 of JP-A-57-136582), 150@1 pyridine, 4 QrLl of methylene chloride , using 31.0 g (163a+mol) of p-toluenesulfonyl chloride and carrying out the same operation as in Example 1 to obtain the title compound 35.
．． 8g was obtained (yield 95%).

IR and NMR spectra were obtained in Example 1 (2S, 3
S.

7R, IIR).

Example 3 370s+g of small metal sodium pieces in 30ml of Nisimi Rimethanol
After adding and reacting and dissolving, 1.48 mZ (16 gmol) of isopropyl mercaptan was added at room temperature, and 30
Stir for a minute. (2S, 3S, 7R, IIR)-2,
A methanol 15N solution of 5.75 g (12 gmol) of 3-epoxy-3,7,11゜15-tetramethylhexadecyl tosylate was added dropwise at room temperature over 20 minutes, and the mixture was heated at 50°C.
The mixture was stirred for 2 hours. After cooling to room temperature, the mixture was poured into 50 ml of cold water and extracted with ether. The extract was washed with water, dried, and the solvent was distilled off to obtain 4.62 g of the title compound (yield quantitative).

The refractive index, IR spectrum, and NMR spectrum of the obtained compound are as follows.

no” 1.4689 IR spectrum: 2930.1460.1380.1
250cm-'NMR spectrum (CC14): δ0
．． 85 (12H, d, J-6Hz).

1.21 (24H, m), 1.27 (6H, d, J=
611z), 2.30-2.77 (3H, m), 2
．． 83 (IH, hept, J=611z) Example 4 The giver also has a 7R11 illusion: “Kan-ni-o”” Shi and Nimu L-engineer 1.
15 2(2R,3R,7R,IIR)-2,3-epoxy-3,7,11,15-tetramethylhexadecyl tosylate 34.2 g (73,3Imono1) and isopropyl mercaptan 7.4 m7 (6 ,1g:80.1+
usol), metallic sodium 1.9g (82,6s
+g atoms), using methanol 150mZ as a solvent,
One operation similar to Example 3 was carried out to obtain the title compound at 27.2
g (yield quantitative).

IR and NMR spectra were obtained in Example 3 (2S.

3S, 7R, IIR).

Example 5 Synthesis of 15-tetramethylhexadecane-3-ol Lithium aluminum hydride 700B (18 mmol) was suspended in 40 mZ of anhydrous tetrahydrofuran, (2S,
3S.

7R,IIR)-2,3-epoxy-3,7,11,1
5-tetramethylhexadecylisoprobyl sulfide 4.62 g (12 mmol) of natohydrofuran 15
Tn! The solution was added dropwise over 15 minutes at room temperature, and then added for an additional 2.5 minutes.
The reaction was carried out under reflux for an hour. After cooling, a 1:1 mixture of tetrahydrofuran and water was gradually added while suppressing heat generation, and 50 n7 of IN hydrochloric acid was further added. After extraction with ether, the organic layer was washed with water and dried, and the crude product was subjected to silica gel column chromatography and eluted with a mixed n-hexane-ethyl acetate system to obtain 3.25 g of the title compound (yield 71%).
.

The refractive index, IR spectrum, and NMR spectrum of the obtained compound are as follows.

n Dzo 1.4718 IR spectrum: 3400.2925.1375.13
60.1150cm+-'NMR spectrum (CC14
)'δ0.89(12)1. d, J=6Hz).

1.15 (31+, s), 1.21 (24H, bs)
, 1.26 (6H, d, J=611z), 2.40
~2.67 (2H, m), 2.88 (IH, hept
, J=6Hz) Example 5' 285 mg (7.5 mmol) of lithium aluminum hydride was suspended in 20-20% of anhydrous tetrahydrofuran, and (25
,3S.

7R,IIR)-2,3-epoxy-3,7,11,1
5-tetramethylhexadecane-1-ol 1.56g
A solution of (5 mmol) in 5 tL of tetrahydrofuran was added dropwise, and the mixture was reacted under reflux for 2.5 hours. Cool to 0℃,
Water was added little by little, 25 m7 of IN hydrochloric acid was added, and the mixture was extracted with ether. The extract was dried and concentrated to obtain a crude diol.

IR spectrum: 3350.2920.1460.1
370 cm-' This crude oil was then dissolved in pyridine 3d, cooled to 0°C, and p-toluenesulfonyl chloride 1,
After adding 33 g (7 m+wol) and stirring for 30 minutes, the mixture was left in the refrigerator overnight. 12 mZ of ice water was added, and the mixture was extracted with methylene chloride. The extract was washed, dried, and concentrated to obtain a crude monotosylate.

IR spectrum: 3500.2920.1360.1
180cm-'115mg of Na in 10nj of methanol
was added to react and dissolve, and 0.0% of isopropyl mercaptan was added.
46mf (5mm+ol) was added. To this solution, add a 5@l methanol solution of the monotosylate compound obtained above,
The mixture was stirred at 50°C for 3 hours. After cooling, it was poured into water, extracted with ether, and purified by column chromatography to obtain the desired product 1.
, 43g was obtained (yield 75%).

IR and NMR spectra were identical to those obtained in Example 5.

Example 6 Lithium aluminum hydride to TIIF 120- 4.
0 g (0,105o+ol) suspended under nitrogen), 26.2g (70,7o+w+o) of the sulfide obtained in Example 4
A 50-THF solution of l) was added dropwise at room temperature over 20 minutes.

The same operation as in Example 5 was carried out to obtain the title compound at 19.9
g (yield 75%).

IR and NMR spectra were obtained in Example 5 (3S.

7R, IIR).

Example 6゜base(2R,3Ri7R,IIR)-2,3-epoxy-3
Example 5
In the same manner as above, 1.4 g of the title compound was obtained (yield 7).
4%).

IR and NMR spectra were identical to those obtained in Example 6.

Example 7 Ac (3S, 7R, IIR) -1-isopropyl 1,000-3.7.11°15-tetramethylhexadecane-3-
All 3.04g (8.1mmol), acetic anhydride 7
．． 6d (81 mmol), pyridine 6.5nZ (8
1 mmol) and 0.21 g (1.7 mmol) of N,N-dimethyl-4-aminopyridine were mixed, and 2
Stirred for 4 hours. After gradually adding methanol, the mixture was poured into 50ml of cold water and extracted with ether. After washing the organic layer with water and drying, the solvent was distilled off, and 4.01 g of the crude product was subjected to silica gel column chromatography.
The title compound 2 was obtained by elution with an isopropyl ether mixture system.
．． 37 g was obtained (yield 94%).

The refractive index, specific rotation, IR spectrum, and NMR spectrum of the obtained compound are as follows.

n o” 1.4647 [α) o” 0.2° (C・9.O, ethanol) (
R spectrum: 2960.1740.1380.13
60cm-'NMR spectrum (CC14): δ0.
85 (12H, d, J-6Hz).

1.17 (29H, m), 1.39 (3H, s),
1.91 (3H, s), 1.83-2.53 (4H,
a+), 2.86 (IH, hept, J=6Hz)
Example 8 (31?, 7R, IIR)-3-acetoxy-3,7,
11,15-tetomethylhexacylisopropylsulfide Hydroxysulfide obtained in Example 4 1.1
2g (3mm+ol), 10mj of acetic anhydride, and 15mg of p-toluenesulfonic acid were mixed and stirred at room temperature for 2 hours, followed by the same operation as in Example 7 to obtain the title compound.
17g was obtained (yield 94%).

IR and NMR spectra were obtained in Example 7 (3S.

7R, IIR).

Specific optical rotation [α] D″0 is +0.94° (C・0.96
, ethanol).

Example 9 Chilphenol person (3S, 7R, IIR) -3-acetoxy-3,7,
A mixture of 1.24 g (3.0 mmol) of 11,15-tetramethylhexadecylisopropylsulfide and 10 m of methylene chloride was cooled to -40°C, and 0.29 m (3.6 mmol) of sulfuryl chloride was added dropwise over 1 minute.
The mixture was stirred at the same temperature for 5 minutes. 4-acetoxy-2,3,5
- A solution of 1.75 g (9+a+ol) of trimethylphenol dissolved in 5-methylene chloride was added dropwise at -40°C over 5 minutes, and the mixture was stirred at the same temperature for 15 minutes. Next, 2.5 m (18 mmol) of triethylamine and 3-methylene chloride
The mixture was added dropwise at -40°C for 3 minutes, and the temperature was gradually raised to room temperature. The reaction solution was poured into water-cooled IN hydrochloric acid 4ON, the organic layer was separated, and the aqueous layer was extracted with hexane. The organic layers were combined, washed with water, dried, and then the solvent was distilled off to obtain the crude product 3.
08g was obtained.

This was subjected to silica gel chromatography, eluted with n-hexane-ethyl acetate mixture system, and the title compound 1.2
(yield: 67%).

The refractive index, IR spectrum, and NMP spectrum of the obtained compound are as follows.

n o” 1.4956 IR spectrum: 3260.2940.1760.1
735.1210 cm-'NMR spectrum (CCIs
): 60.87 (12H, d, J=6Hz).

1.18 (30t1.bs), 1.83 (3H,s)
, 2.01 (3H, s).

2.09 (3H, s), 2.17 (3H, s), 2
．． 25 (38, s), 1.8-2.9 (311, m)
, 4.57 (lfl, t, J-5Hz), 7.56
(IH,s) Example 10 Synthesis of thylphenol (3R,7R,IIR) -3-acetoxy-3,7,
Using 1.24 g (3.0 mmol) of 11,15-tetramethylhexadecylisopropylsulfide, the title compound was prepared in the same manner as in the synthesis of the (3'S, 7°R111''R) compound in Example 9. 1.25g was obtained (yield 6
9%).

IR and NMR spectra were obtained above (3'S, ?
“R911′ R) was identical to that of the compound.

Example 11 (3'S, 7'R, 11"R)-4-acetoxy-2-
(3°-acetoxy-1′-isopropylthio-3°,
? ', 11".

15'-tetramethylhexadecyl) -3,5,
6-trimethylphenol 39g (0.64mmol
) in a small amount of ethanol, Raney nickel (-4
) and heated under reflux for 75 minutes, nickel was then filtered off, the solvent was distilled off, and the mixture was subjected to silica gel chromatography to obtain 306 mg of the title compound (yield: 90%).

The IR spectrum and NMR spectrum of the obtained compound are as follows.

IR spectrum: 3300.2940.1760.1
735cm-'NMR spectrum (CC1,): δ0
．． 86 (12H, d, J=6Hz).

1.17 (3011, bs), 1.85 (3H, s)
, 1.95 (311, s).

2.02 (3H, s), 2.09 (3H, s), 2
．． 19 (311, s), 1.8-2.9 (411, m
), 7.41 (IH, s) Example 12 (3'R, 7'R, 11'R) -4-acetoxy-2
-(3°-acetoxy-1”-isopropylthio-3’
, 7', 11°.

15゛-tetramethylhexadecyl') -3,5
,6-trimethylphenol 503mg (0,83o+
The title compound 397n+g was obtained in the same manner as in Example 11 using (yield: 90%).

IR and NMR spectra were identical to those obtained above.

Example 13 Lithium aluminum hydride 15 g (3.9 mmol
) in 10 m7 of ether, (3'S, 7"
R111°R)-4-acetoxy-2-(3”-acetoxy-3°, 7”.

11°, 15”-tetramethylhexadecyl) -3
, 5,6-trimethylphenol 303 mg (0,57
A solution of m+wol) dissolved in ether 10- was added dropwise at 0°C, and the mixture was stirred at room temperature for 1.5 hours. Thereafter, ether saturated with water was added under cooling, IN hydrochloric acid 10- was further added to separate the organic layer, and the aqueous layer was extracted with ether. The organic layers were combined, washed with water, dried, and the solution was concentrated to about 10 m7. Lead dioxide 600B was added and stirred at room temperature for 3 hours. The reaction solution was filtered, the solvent was distilled off, and the crude product was purified with silica gel. Subjected to column chromatography, the title compound 2
29B was obtained (yield 90%).

Specific rotation, IR spectrum and NMR of the obtained compound
The spectrum is shown below.

[α) o” +1.0” (C・10.0. Ethanol) IR spectrum: 3450.1640ca-
'NMR spectrum (CC14): 60.87 (1
2H, d, J=6Hz).

1.17 (23B, bs), 2.00 (611, s)
, 2.03 (3B, s).

1.8-2.8 (5f1.m) Example 14 (3'R,7"R111"R)-4-acetoxy-2-
(3°-acetoxy-3', ?', 11', 15'
Using 319+wg (0.60 mmol) of -tetramethylhexabcyl)-3,5,6-)limethylphenol, the same procedure as in Example 13 was carried out to obtain 238 mg of the title compound.
was obtained (yield 89%).

[α)D” 1.0° (C=10.0. ethanol) rR and NMR spectra were identical to those obtained above.

Example 15 (3'R,?'R,11''R)-2-(3'-hydroxy-3+,7+.

11', 15° -tetramethylhexadecyl') -
3,5,6-drimethyl-1,4-benzoquinone 223
s+g (0.50 mmol) was dissolved in ethyl acetate 20+nZ, 100 mg of 5% palladium/carbon catalyst was added, and the mixture was shaken at room temperature in a hydrogen stream. When hydrogen absorption ceased, the catalyst was filtered off and the filtrate was concentrated under reduced pressure. The obtained oil was dissolved in benzene 10-, 9 mg of pt-luenesulfonic acid was added, and the mixture was refluxed for 1 hour. Then, 5 rnl of a saturated aqueous sodium bicarbonate solution was added, the organic layer was separated, and the aqueous layer was dissolved in ether. Extracted. The organic layers were combined, dried, and then the solution was distilled off, and the crude product was subjected to silica gel column chromatography to obtain 194 mg of the title compound (yield 90%).

Specific rotation [α]D' of the obtained compound. is -2.7° (
C・5.0. benzene). Also, IR and NMR
The spectra matched perfectly with those of the standard sample.

In alkalinity +Fe(CN) bSpecific rotation of the oxidized dimer [α]. " is +32" (C・0.17, isooctane) (literature value [α]. "+31.5° (C-5, isooctane)), indicating that it is optically pure d-α-tocopherol. confirmed.

Practical Example 16 Desulfurizer 390+wg (0.8 molar o1) obtained in Example 12
) was dissolved in ether 20 -, and 15 g (3,9+++ mol) of lithium aluminum hydride was dissolved in ether 10
The mixture was added dropwise at 0° C. to the suspension in - and stirred at room temperature for 1.5 hours.

Thereafter, ether saturated with water was added under water cooling, and 10-IN hydrochloric acid was further added to separate the organic layer, and the aqueous layer was extracted with ether. The organic layers were combined, washed with water, dried, and then the solvent was distilled off. The obtained oil was dissolved in 10-benzene and 15-g of p-1-luenesulfonic acid (0.08 mmol) was dissolved in 10-benzene.
1) was added and the mixture was refluxed for 1 hour. Thereafter, a saturated aqueous sodium bicarbonate solution 5- was added to separate the organic layer, and the aqueous layer was extracted with ether. The organic layers were combined, dried, and then the solvent was distilled off, and the crude product was subjected to silica gel column chromatography to obtain 280+ mg of the title compound (yield 90%).

Specific rotation [α] of the obtained compound Dzo is -2,7'
(C.5.0.benzene). Also, IR and NM
The R spectrum was the same as that obtained in Example 15.

Example 17 (2R, 4'R, 8°R)-α-tocopherol (3) (3'S, 7''R911°R)-2-(3'-
Hydroxy-3Z? +.

11", 15"-tetramethylhexadecyl")
-3,5,6-drimethyl-1,4-benzoquinone 22
3 mg (0.50 mol) was dissolved in 20-ethyl acetate, 100 mg of 5% palladium/carbon catalyst was added, and the mixture was shaken at room temperature in a hydrogen stream.

When hydrogen absorption ceased, the catalyst was filtered off and the filtrate was concentrated under reduced pressure. The obtained oil was dissolved in 20nj of n-hexane, 1.0g of anhydrous zinc chloride was added, the solvent was distilled off under reduced pressure, and the residue was heated to 50°C for 1.5 hours.

In the future, we will add water to decompose, extract with ether, and extract 3
It was washed successively with N hydrochloric acid and water and dried. The solvent was distilled off under reduced pressure, and the crude product was subjected to silica gel column chromatography to obtain 150 mg of the title compound (yield 70%).

Specific rotation [α]D' of the obtained compound. is -1.8° (
C=5.0. benzene). Also, IR and NMR
The spectrum was identical to that obtained in Example 15.

Example 18 (2S, 4''R, 8'R)-α-tocopherol person'
(1) 300 mg (0.56 m
mol) and operated in the same manner as in Example 16 to obtain 235 mg of the title compound (yield 90%).

IR and NMR spectra are (2R, 4'R, 8'R)
-It was the same as α-tocopherol. Specific optical rotation [α]
Dt.

was +0.9° (C=0.5.benzene).

Example 19 (234'R,8'R-α-tocopherol)
Using 200 mg (0.45 mmol) of (3°S)-α-tocopherylquinone obtained in Example 13, the same procedure as in Example 15 was carried out to obtain 170 mg of the title compound (yield: 8
8%).

The IR and NMR spectra of the obtained compound were identical to those obtained above.

Claims (1)

[Claims] 1 Structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) [In the formula, R_1 represents ▲There are mathematical formulas, chemical formulas, tables, etc.▼. The same applies below] Or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I') The compound represented by is tosylated with p-toluenesulfonyl chloride, and the structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) [ In the formula, Ts represents a tosyl group (▲numerical formula, chemical formula, table, etc.▼). The same applies below] Or ▲ There are mathematical formulas, chemical formulas, tables, etc.▼ Obtain the compound represented by (II'), and then react the compound with isopropyl mercaptan in the presence of metallic sodium to obtain the structural formula: ▲ Numerical formula, chemical formula, There are tables, etc. ▼ (III) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III') Obtain the compound represented by, then reductively cleave the compound, structural formula: ▲ Numerical formulas, chemical formulas, tables, etc. There is a compound represented by ▼ (IV) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV') Then, by acetylating the compound, the structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( V) [In the formula, Ac represents an acetyl group. The same applies below] or ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Obtain a compound represented by (V'), and then react the compound with 4-acetoxy-2,3,5-trimethylphenol to obtain the structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VI) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VI') Obtain the compound represented by, and then react the compound with Raney nickel and further deacetylate it to obtain the structural formula : ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VII) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VII') Obtain the compound, and then directly cyclize the compound or oxidize it. Structural formula characterized by cyclization after obtaining α-tocopherylquinone: ▲Mathical formula, chemical formula, table, etc.▼(VIII) (2R, 4'R, 8'R)-α- Tocopherol or structural formula: ▲ Numerical formula, chemical formula, table, etc. ▼ (VIII') Method for producing (2S, 4'R, 8'R)-α-tocopherol. 2 Structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) [In the formula, R_1 represents ▲There are mathematical formulas, chemical formulas, tables, etc.▼. The same applies below] Or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( I ') By reductively cleaving the compound represented by: Structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IX) or ▲ Mathematical formulas, There are chemical formulas, tables, etc.▼(IX') Obtain the compound represented by, and then tosylate the compound with p-toluenesulfonyl chloride to obtain the structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(X) In the formula, Ts represents a tosyl group (▲numerical formula, chemical formula, table, etc.▼). The same applies below] Or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Obtain the compound represented by (X'), and then react the compound with isopropyl mercaptan in the presence of metallic sodium to obtain the structural formula: ▲ Numerical formula, chemical formula, There are tables, etc. ▼ (IV) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV') Obtain the compound represented by, and then acetylate the compound to obtain the structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼(V) [In the formula, Ac represents an acetyl group. The same applies below] or ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Obtain a compound represented by (V'), and then react the compound with 4-acetoxy-2,3,5-trimethylphenol to obtain the structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VI) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VI') Obtain the compound represented by, and then react the compound with Raney nickel and further deacetylate it to obtain the structural formula : ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VII) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VII') Obtain the compound, and then directly cyclize the compound or oxidize it. Structural formula characterized by cyclization after obtaining α-tocopherylquinone: ▲Mathical formula, chemical formula, table, etc.▼(VIII) (2R, 4'R, 8'R)-α- Tocopherol or structural formula: ▲ Numerical formula, chemical formula, table, etc. ▼ (VIII') Method for producing (2S, 4'R, 8'R)-α-tocopherol.