JPH0273026A - Production of panaxacols - Google Patents

Abstract

PURPOSE:To obtain the subject substance useful as a low-toxic carcinostatic agent in high stereoselectivity and yield by reacting an epoxy alcohol derivative with a diyne compound in the presence of a base and treating the reaction product with an acid. CONSTITUTION:The objective compound of formula IV can be produced by reacting a compound of formula I (R<1> is tetrahydropyranyl or trialkylsilyl) with a compound of formula II (R<2> is same as R<1>; R<3> is ethyl, vinyl, 2- chloroethyl or 2-chloro-1-hydroxyethyl) in a solvent (e.g. THF) in the presence of a base (e.g. butyllithium) at -20-0 deg.C for 3hr and deprotecting the resultant compound of formula III with an acid (e.g. hydrochloric acid or p-toluenesulfonic acid) at 0-20 deg.C for 0.5-1hr. the compouhd of formula IV can be extracted from the rhizome or callus of Panax ginseng, however, the content is small.

Description

Detailed Description of the Invention (Technical Field) The present invention relates to the use of Panax ginseng (Panax, ginseng).
ngC,A,? dihydropanaxacol (dihydropanaxacol), a diyne compound extracted from the roots or callus of P.
The present invention relates to a new method for synthesizing ropanaxacol and its analogues.

(Prior art) Conventionally, cancer chemotherapy agents include alkylating agents (nitrogen mustard, ethyleneimines, sulfonic acid esters), antimetabolites (folate antagonists, purine antagonists,
pyrimidine antagonists), plant pre-fission (colcemid, vinblastine, etc.), antibiotics (sarcomycin, carcinophilin, mitomycin, etc.), hormones (adrenal steroids, male hormones, female hormones), and porphyrin complex salts (marphyrin, C0PF) etc. are used.

However, most of them are cytotoxic substances,
Because they exhibit serious side effects, there is a desire to develop anticancer agents with low toxicity and excellent anticancer activity.

In view of the above-mentioned purpose, the present inventors searched for a substance with low toxicity and anticancer activity from a wide range of organisms in the ginseng, plant, and microbial worlds. They discovered that diyne compounds have excellent anticancer activity and extremely low toxicity, and filed a patent application for this invention (Japanese Patent Application No. 50067/1982).

However, there was a problem in that in vivo activity tests could not be conducted due to the low content of polyacetylene derivatives in callus.

(Problem H to be Solved by the Invention) Therefore, an object of the present invention is to make it possible to supply a large amount of polyacetylene derivatives by chemical synthesis.

(Means for Solving the Problem) The present inventors have discovered that by selecting tartaric liquor ester as a synthetic raw material, the target dihydrovanaxacol and its analogues can be synthesized stereoselectively and with high yield. We found this and were able to solve the above problem.

That is, the present invention provides a compound (A> 1t (A) (in the formula, R1 represents either a tetrahydropyranyl group or a trialkylsilyl group) and a compound (B) R3-CH-C=C-C= CH R2 (B) (In the formula, R2 represents either a tetrahydropyranyl group or a trialkylsilyl group, and R3 represents any of an ethyl group, a vinyl group, a 2-chloroethyl group, and a 2-chloro-1-hydroxyethyl group. An object of the present invention is to provide a method for producing a compound (C) by reacting the compound (C) in the presence of a base.

Dihydrobanaxacol, which is a typical compound synthesized by the method of the present invention, is a compound described in Examples on page 223 of JP-A-62-207234, and has the following formula (in the formula , R1 and R2 each represent either a tetrahydropyranyl group or a trialkylsilyl group, and R' represents either an ethyl group, a vinyl group, a 2-chloroethyl group, or a 2-chloro-1-hydroxyethyl group. ) is produced, and then treated with acid to produce compound 1) (4,6-hebutadecadiine-3,
9,10-triol) and has the following physicochemical properties.

(a) Form of substance: colorless oily substance 254sh (364), 266sh (358)
.

282sh (238) CHCβ.

(C) IRL'max Cm-': 3560 (
w), 3350(w), 2910(s).

2850 (01), 2220 (w), 14
50 (m).

1370(w) (d) MS m/e: 280(!J”)(e)
' H-NMR (CDCI! 3. 400MHz, δ
): 0.88(3) l, t, J=7Hz), 1.
02 (3H, t, J=7Hz) 1, 30 (br),
1.50 (LH, br) 1.74 (2
H, br), 2.57 (IH, dd, J=6.15
Hz) 2.59 (3H, dd, J=6.15Hz),
3.59(1)1. m).

3,65 (IH,m), 4.37 (1
)1. t, J=6)1z) The present invention is characterized in that dihydropanaxacol and its analogues having such a characteristic diyne structure are synthesized from two components.

That is, for example, dihydropanaxacol (I) is characterized in that it is synthesized from 0 parts of the following components.

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

■0 part obtained from the propatool part and ■diyne part, and CH3CH,C obtained from the glycol part and ■hexyl part.
HO Scheme 2 HC=C-["miCH Scheme 3 Scheme 1 (continued) ■ Each reaction shown in the above scheme will be explained in detail below.

(a) The tartaric acid ester used as a raw material for the synthesis of ketal (2) may be either an ester of L-tartaric acid or an ester of D-tartaric acid, and depending on the configuration of the tartaric acid ester used, the final dihydrovanaxacol may be formed. The three-dimensional configuration is determined. When an ester of D-tartaric acid is used, the steric configuration of the glycol moiety of dihydrovanaxacol obtained is the same as that of natural vanaxacol. The ester may be an ester such as benzyl in addition to an alkyl ester, and the diester does not have to be an ester derived from the same alcohol. That is, asymmetric tartaric acid esters can also be used. In particular, it is preferable to use L-(+)-diethyl tartrate or D-(-)-diethyl tartrate.

Examples of reagents that can be used for ketalization include cyclohexanone, acetone, methyl ethyl getone, etc., and it is particularly preferable to use acetone dimethyl acecool. When using an acid catalyst, camphorsulfonic acid (C3A), para-toluenesulfonic acid (
TsOH), pyridinium valatoluenesulfonate (PPTS), and the like can be used. As the solvent, solvents commonly used for ketalization, such as benzene and toluene, can be used, but it is not necessary to use a solvent, and the reaction can be carried out usually at a temperature in the range of 20°C to 150°C.

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

(b) Synthesis of diol (3) To convert diester (2) to diol (2),
Lithium aluminum hydride (L
iA j' H,), lithium borohydride (Li
The reaction can be carried out using an ester reducing agent such as BH4), usually at -20°C to 50°C, and the desired product (3) can usually be obtained in a yield of 80% or more.

(c) Introduction of leaving group ((3) → (4)) Diol (3)
Valatoluenesulfonyl M (p
-Ts group) or methanesulfonyl group (\IS group), the corresponding baratoluenesulfonyl chloride (p-TsCl) or methanesulfonyl chloride (M
sCβ) and the like in 1. for (3).
A leaving group can be selectively introduced into one of the hydroxyl groups in (3) by reacting 0 mol to 1.2 mol, preferably 1 mol. By using pyridine, collidine, etc. as a solvent and reacting at θ°C to 25°C for 5 hours, the target (4) can be obtained with almost no by-products reacted with both hydroxyl groups.

(d) Introduction of protecting group ((4)→(5)) The unreacted hydroxyl group in compound (4) is preferably protected with a commonly used hydroxyl protecting group.

Protective groups that can be used include those that easily form a hydroxyl group in the presence of an acid, such as a tetrahydropyranyl group (
(THF group), trialkylsilyl group, etc. In order to introduce a protecting group, (4) may be reacted with a corresponding compound such as dihydropyran (DHP) or trialkylsilyl chloride, and in this reaction, CAS or the like may be used as an acid catalyst. The desired hydroxyl group-protected product (5) can be obtained by reacting at 0°C to 25°C using dichloromethane, chloroform, etc. as a solvent.

When a THF 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 it is not possible to proceed with subsequent reactions as a mixture. can.

(e) Hexylation ((5) → (6)) Compound (5) can be n-hexylated by a nucleophilic reaction to obtain hexyl compound (6). Reagents that can be used for hexylation include n-hexyl copper lithium,
Metal hexyl compounds such as n-hexyllithium can be mentioned. These reagents at -20°C to 0°C,
The reaction can be carried out in an anhydrous solvent such as anhydrous half-hydrol or anhydrous THE, preferably under a stream of an inert gas such as nitrogen. A particularly preferred hexylating agent is n-hexyl steel lithium, but it is preferred that the reagent be prepared at the time of use.

(f) Synthesis of triol (7) To obtain triol (7) from hexylated compound (7), for example, in the presence of an acid such as hydrochloric acid, sulfuric acid, para-toluenesulfonic acid, etc., a solvent such as methanol, ethanol, etc. The reaction can be carried out inside. The reaction is carried out at 0°C to 20°C, usually 0.5
(7) can be obtained in good yield by carrying out the reaction for 1.0 hours.

(g) Introduction of leaving groups ((7) → (8)) As suitable groups as leaving groups, the leaving groups listed in () 1) above can be used, and they can be used in combination with the above-mentioned reagents. It can be easily introduced.

The amount of reagent is 1.0 mol to 1.2 mol, and 0 to 2 mol.
By reacting at 5° C. for 5 hours, a leaving group can be selectively introduced into the terminal hydroxyl group, yielding (8).

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

(1) Introduction of protecting group ((9) → αO) It is preferable to protect the hydroxyl group of the obtained (9), but the protecting groups listed in 2) can be suitably used as the protecting group. . Introduction of a protecting group can also be carried out by the method described above, and a hydroxyl group-protected product αQ can be obtained.

(NU) Diyne compound α■ and protected form 0 lydiacetylene 0
A diyne compound can be obtained from (2) and propionaldehyde, acrolein, etc. in the presence of a base by a conventional method.

THF as solvent.

Dimethoxyethane, etc. may be used, and butyllithium (hexane solution), methyllithium, etc. may be used as the base.
The reaction may be carried out at -20°C to 0°C for 1 hour. Obtained 0
In (2), it is preferable to protect the hydroxyl group, and as the protecting group, the protecting groups listed in (d) can be suitably used. The introduction of the protecting group can also be carried out by the method described above, and the protected compound can be obtained in good yield.

(l) Compound 0ω Compound 0 can be synthesized from the obtained compound α and compound Q4). Compound 04) is treated with a base such as butyl lithium (hexane solution), Grignard reagent, sodium hydride, potassium amide, etc. in a solvent such as THF or dimethoxyethane to form a metal acetylide, and then α0 is converted into a metal acetylide, preferably in THF or the like. It can be added by dissolving it in a solvent. The reaction is preferably carried out at -20°C to 0°C, and by reacting for about 3 hours, an adduct of ring-opened epoxy can be obtained.

(w) Protecting group (05)→(1)) To remove the protecting group, the method described in (f) can be used. The desired dihydrovanaxacol can be obtained by deprotection.

(Effects of the Invention) The novel synthesis method of the present invention has made it possible to synthesize large amounts of dihydrovanaxacol and its analogues, which were conventionally obtained in extremely small amounts through extraction.

Next, the present invention will be explained with reference to Examples.

(Example) Example 1 ((1)→(2)) L-(+)-diethyl tartrate (1) 11.0
g to acetone dimethyl acetal (2,2-dimet
hoxypropane) 50-, add 100 mg of camphorsulfonic acid (C3A), and dissolve in 50-
Stir overnight in a 70°C oil bath. Refrigerator, ethyl acetate 10
Add 0zo, 5% NaHc○, solution 50ml! The organic layer was separated. The aqueous layer was extracted with ethyl acetate and combined with the organic layer, washed twice with saturated brine,
It was dried and concentrated. The resulting mixture was subjected to silica gel column chromatography (hexane: ethyl acetate = 3: 1).
(2) (9.0 g, yield 6 g, 5%) was obtained and 15% of the raw material was recovered.

Example 2 ((2)→(3)) LiAji! in 100 ml of anhydrous ether! 46.0 g
was added with stirring to form a suspension, and then compound (2) (7
, 7 g) in ether (40 ml) was slowly added dropwise thereto, and the mixture was stirred overnight at room temperature. Then 20ml of ethyl acetate
was added dropwise and stirred for 30 minutes, followed by 30 r of saturated Rochelle salt solution.
n1 was added, and the mixture was filtered and condensed using Celite as a filter aid. The obtained oil was subjected to silica gel column chromatography (hexane:ethyl acetate = 3 = 1 and 1:2) to obtain compound (3) (3.7g, yield 77%). The obtained (3) was obtained by Mori and S. Tanada.
(Tetrahedron volume 35 + pages 1279-1284, 1
The NMR spectrum matched that of the compound reported in 1999).

Example 3 ((3)→(4)) Pyridine solution (30 ml) of compound (3) (3.2 g)
), para-toluenesulfonyl chloride (pTsCj
! 3.0 g) was added and left overnight at room temperature. Then,
Saturated salt water LOOm7! and extracted with ethyl acetate,
Concentration under reduced pressure gave an oily substance. This oily substance was subjected to silica gel column chromatography (hexane:ethyl acetate=2:1) to yield compound (4) (3.4 g).

A yield of 54.5% was obtained and 10% of the raw material was recovered.

' H-NMR1,35 (S) (ppm 1.38 (S) 2.2
0 (br, s) 2,45 (S) 3.74 (m) 4.15 (m) 7.35 (d, J=8.3Hz) 7.77 (d, J=8.3)+2) Example 4 ((
4) → (5)) Compound (4) (1.7 g) in dichloromethane solution (1
0 mil”), 3,4-dihydro 1:l-2H-bira:
/(DHP.

679 mg, 1.5 equivalents) and 50 mg of C3A were added and stirred at room temperature for 30 minutes. After the reaction is complete, add 50ml of ethyl acetate.
After adding j', the mixture was poured into saturated NaHCOa water and extracted with ethyl acetate. Next, the organic layer was diluted with saturated saline (5
0mf! Wash twice with
The oily substance obtained by drying and concentrating was subjected to silica gel column chromatography (hexane: ethyl acetate = 3: 1),
Compound (5) (2.0 g, yield 93.0%) was obtained.

'H-N, MR1,35 (S) (ppm) 1.38 (s) 1.57 (br, s) 2,45 (s) 3.52 (br, m) 3.57 (br, m) 4.14(m) 4.6Hbr, s)? , 34(d, J=8.3)1z) 7.81(d, J=8.3Hz) Example 5 ((5)→(6)) Cupric iodide <1.34g, 3. Oeq ) was suspended in anhydrous ether (25mj?) and cooled to -40°C. Then, n-hexyllithium-ether 2) (4
,5mj! , l, 55 mmol/m) was added dropwise, and 15
The mixture was stirred for a minute (at this time, the color of the reaction liquid was pale yellow, but gradually changed from brown to blackish brown). Furthermore, n-hexyl lithium/ether 2) 4.5 m! ! (1,56m
m01/mj') was added dropwise and stirred for 15 minutes.The color of the reaction solution changed from dark brown to pale purple to deep blue-purple.)
. Next, an ether solution (8 ml) of compound (5) (930 mg) was added dropwise over 10 minutes at a bath temperature of -30°C. (As the dropwise addition progressed, the color of the reaction solution changed from deep blue-purple to black. ). After further stirring at this temperature for 1 hour, saturated ammonium chloride solution (10rrLl) was added and stirred for 20 minutes.Then, this mixture was extracted with ether, and after washing twice with saturated brine (30ml), Na2S04 The obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate = 7:1), and then further purified by HPLC (Nucleosil 5Q-
5,8X 3 Q Q mm.

Hexane:ethyl acetate = 20:1, 3.0 m
/m1n) to obtain compound (6) (500mg,
A yield of 66.4% was obtained (eluting at 17 minutes).

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

2) Metallic lithium (30%) disversion 11.8
g, 2.5 eq.) in anhydrous ether (60 ml') and stirred. ,, n-Bromhexane (3 ml, about 1/3 of the total amount used) was added and stirred at room temperature, and when the internal temperature rose, the mixture was cooled to -15°C. Then, the remaining n-bromohexane (25 mN) was gradually added, and the mixture was further stirred at -15°C for 3-4 hours. The obtained hexyllithium solution was left standing in a refrigerator, and the titer of the supernatant ether layer was assayed with 5ec-butanol (indicator: 1,10=phenanthrylon), and then used for the reaction.

Rf (hexane:ethyl acetate=7:l, silica gel thin layer chromatography, Merck & Co., Ltd. Art.

5715.0.25mm (same in the following examples) =
0.33 Example 6 ((6) → (7)) Methanol solution (4 m
2N-HCl (1 rnl) was added to the mixture and stirred at room temperature for 1 hour. Next, 40rrLl of ethyl acetate was added, and after washing twice with saturated saline (10mf'), N a 2 SO
4 and concentrated to obtain compound (7) (206 mg, yield 88.0%) as colorless crystals.

H-N! , (RO,95(t, J=7.1Hz)(9
11m) 1.2-1.4 (br, m)1
, 50 (m) 3,62 (m) 3,75 (m) ”C-Nλ(R14,1,22,7,25,8,29,
4 (ppm) 29.8. 31.9. 3
3.6. 64.572.4. 74.3゜m, p, 48℃ IR(CHCj2*)cm-';3400(''), 2
925(s), 28+0(m) Example? ((1
) → (8)) Pyridine solution (2 ml') of compound (190 mg)
(p-Tsi)
(185 mg) was added and left to stand at room temperature.

Add saturated brine (30d), extract with ethyl acetate,
The organic layer was dried with Na 2 S Oa and concentrated.

The obtained mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 3:1), and compound (8) < 150m
g, yield 43.6%) was obtained as colorless crystals.

H-NMR0,88 (t, J=7.3Hz) (pp
m) 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)1z) 7.80 (d,
J=8.1Hz) m, p, 63℃ rR (cm-'); 3550 (m), 29
25 (s>, 2850 (m).

1730 (m), 1600 (m), 1460 (
m) Example 8 ((8)→(9)) Methanol solution of compound (8) (114 mg) (3,
Anhydrous potassium carbonate (457 mg, 10 equivalents) was added to 5-) and stirred at room temperature for 1 hour. Saturated brine (40rnl) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over Na2SO4, and concentrated. The resulting mixture was subjected to silica gel chromatography (hexane:ethyl acetate = 2:1) to obtain compound (9) (
550 g, yield 75.5%) was obtained.

H-NMR0,88 (t, J=7.3Hz) (pp
m) 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=4.9Hz) 2.9g(m) 3,44 (m) IR(c+n-ri; 3600(w), 350
0(w), 3430(s).

3360 (m) Example 9 ((9) → αQ) Dichloromethane solution of compound (9) (50 mg) (1,
5m1. ) DHP (40 μm) and a trace amount of C3A were added, and the mixture was stirred at room temperature for 30 minutes. Next, the reaction solution was added with Na
HCO3 solution (20ml) was added and extracted with ethyl acetate.The organic layer was washed with saturated brine, and then Na2S
It was dried over Oa and concentrated. The resulting mixture was subjected to silica gel chromatography (hexane:ethyl acetate = 3:1) to obtain compound α (167 mg, yield 9o, 0%).

Rf (hexane:ethyl acetate=5:1) =0.
40.0.47 (Diastereomer mixture) 'H-NMRO, 88 (t, J=7.3Hz) (1)
I) m) 1.2-1.4 (br, m) 15
~1.7 (br, m) 1,76 (+n) 1.84 (m) 2.49 (dd, J=2.7.4.9Hz) 2.67
(dd, J=2.7.4.9)1z)2.76(t,
J=4.9)1z) 2.80(t, J=4.9)1z) 2,95 (m) 3,09 (m) 3,38 (m) 3,50 (m) 3,88 ( m) 4,00 (m) 4.70 (t, J=4.4Hz) 4.98 (t, J=4.4Hz) Example 10 ((Company) 100 → 0 ■ → α4)) Di THF solution on the acetylene surface (15 mj (1 mmo 17 m
l) was cooled to -50°C and stirred. To this was added butyllithium-hexane (10-11.5 mmol/ml) and propionaldehyde ((6), 840 mg).

14.5 mmol) was gradually added dropwise, and the mixture was further stirred for 30 minutes. Next, 50 ml of saturated ammonium chloride solution was added and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over Na 2 SO 4 and concentrated. The resulting mixture was chromatographed on silica gel (hexane). After separation and purification with ethyl acetate = 5:1), dissolved in dichloromethane (10rrf), DHP (1 ml) and C3A
(20 mg) was added and stirred at room temperature for 1 hour. A Na HCOs solution (20 ml) was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with saturated brine, then diluted with Na2S○.
, and concentrated. The resulting mixture was subjected to silica gel chromatography (hexane: ethyl acetate = 7: 1),
Compound α4) (1.4 g, yield 50.0%) was obtained.

Rf (hexane:ethyl acetate=5:1) =0.
60.0.68 (diastereomeric mixture) 'H-N! , IR1,00 (t, J・7.3Hz) (
ppm) 1.04 (t, J=7.3)1z
) 1,56 (m) 1,78 (m) 2.14 (d, J=0.9tlz) 2.15 (d, J=0.9Hz) 3.54 (m> 3,80 (m) 4 , 00 (m) 4.25 (t, J=6.4Hz) 4.41 (t, J=6.4Hz) 4.74 (t, J=3.4H2) 4.93 (t, J=3 .4flz) Example 11 (α[] + Q4)→0) Compound α4
) (77 mg, 0.4 mmol) in THF solution (130
μl) to -30°C, butyllithium-hexa7
(230AII, 0.3 mmol) and HMPA
(50 μl, 0.3 mmol) was gradually added dropwise.

Then, a THF solution (100 μm) of compound α (1 (25 mg, O, 1 mmol)) was added dropwise and stirred at −30° C. for 2 hours. After the reaction was completed, a saturated N H, C1 solution (10 m
and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over Na 2 SO 4 and concentrated.

The resulting mixture was subjected to silica gel chromatography (hexane:ethyl acetate = 5:1) to obtain a compound layer (20 mg).

A yield of 44.4% was obtained.

Rf (hexane:ethyl acetate=5:1) =0.
22.0.26 (diastereomer mixture) Example 12 (QS-7 history) Methanol solution (500 μm) of compound side (10 mg)
A trace amount of C3A was added to the mixture, and the mixture was stirred at room temperature for 1 hour. Next, ethyl acetate (10 rnl) was added and the mixture was washed with saturated brine, dried over Na*SO, and concentrated.

This was analyzed using HP LC (Nucleosil 50-5.
8 x 300 mm.

hexane:εtO^c=2: L, 3.0m
j! /min) to separate and purify compound (1) (4 mg,
A yield of 64.5% was obtained (eluting at 22 minutes).

'H-NMRQ, 89(t, J=7.1Hz>(pp
m) 1. OHt, J=7.3Hz)1.
2 to 1.4 (br, m> 1, 50 (m) 1.74 (m) 2.57 (dd, J=6.4. 16.9Hz) 2
．． 59<dd, J=5.6. 16.9Hz)3,
58 (m) 3, 63 (m) 4.35 (t, J=6.4)1z)IR(C)lc
J,) cm-'; 3600 (w), 2930
(s) 2860 (m), 2260 (w) [
α) = -17.0 Compound (1) obtained in this example was compared with dihydropanaxacol obtained by reducing naturally-obtained panaxacol. The following method was used to reduce vanaxacol.

Panaxacol (74 mg) in methanol (1,0-)
and excess NaB H4 was added with stirring. After about 30 minutes, saturated saline (Lornl) was added and extracted with ethyl acetate. After drying the extract with Na 2 SO and concentration, the resulting oil was analyzed by HPLC (Nuc
leosil 50-5. 8 X 300111[0
, hexane:ethyl acetate=1:1) to obtain dihydropanaxacol (60 mg, 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. It was confirmed that compound (1) is dihydropanaxacol.

Claims (1)

[Claims] Compound (￥A￥) ▲Mathematical formulas, chemical formulas, tables, etc.▼ (￥A￥) (In the formula, R^1 represents either a tetrahydropyranyl group or a trialkylsilyl group. ) and compounds (¥B¥) ▲Mathematical formulas, chemical formulas, tables, etc.▼ (¥B¥) (In the formula, R^2 represents either a tetrahydropyranyl group or a trialkylsilyl group, and R^3 is ethyl group, vinyl group, 2-chloroethyl group, or 2-chloro-1-hydroxyethyl group) in the presence of a base to form a compound (¥C¥)▲mathematical formula, chemical formula, table, etc. ▼ (￥C￥) (In the formula, R^1 and R^2 each represent a tetrahydropyranyl group or a trialkylsilyl group, and R
^3 is ethyl group, vinyl group, 2-chloroethyl group, 2-
Indicates any chloro-1-hydroxyethyl group. ) After producing compound ￥(1), by treating with acid
￥▲There are mathematical formulas, chemical formulas, tables, etc.▼ ￥(1)￥ (In the formula, R^3 represents either an ethyl group, a vinyl group, a 2-chloroethyl group, or a 2-chloro-1-hydroxyethyl group. ).