JP3441488B2 - New saponin compounds and desacyl saponin compounds - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel saponin compound and a desacylsaponin compound. More specifically, isolated from tea (Thea sinensis L.) leaves,
The present invention relates to a novel saponin compound and a desacylsaponin compound having an antiallergic action and useful as a medicine.

[0002]

2. Description of the Related Art Regarding saponins obtained from tea seeds, two new types of saponins (theasaponin E ₁ and theasaponin E ₂ ) have already been isolated and their chemical structures have been clarified (Pharmaceutical Journal 112 , 1-41). Page, (1992)
reference). On the other hand, tea leaf saponin was separated as a mixture, and its UV spectrum, optical rotation, and other data have revealed that it is different from tea seed saponin (Agricultural Chemical Society, 43 , 750-757, (1969).
reference). The structure of tea leaf saponin has not been clarified yet because isolation and purification of tea leaf saponin is difficult.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a new saponin compound. Another object of the present invention is to provide a novel saponin compound obtained from tea leaves. Still another object of the present invention is to provide a novel saponin compound having anti-inflammatory and anti-allergic effects and useful as a pharmaceutical. Still another object of the present invention is to provide a novel desacylsaponin compound obtainable from the novel saponin compound of the present invention.
Further objects and advantages of the present invention will be apparent from the following description.

[0004]

According to the present invention, firstly, the above objects and advantages of the present invention are represented by the following formula (1):

[0005]

[Chemical 3]

By a new saponin compound represented by
To be achieved. The novel service of the present invention represented by the above formula (1)
Ponine compound (hereinafter theasaponin B ₁Is)
Shows physical properties. (1a) Optical rotation [α]_D ²⁰= -14 ° (C = 0.8, meta
Noor) (2a) Infrared absorption spectrum (KBr diffuse reflection method) It is shown in FIG. In Figure 1, Peak 1 ... 3381 cm^-1, Peak 2 ... 2951 cm^-1, Peak 3 ... 1728 cm^-1, Peak 4 ... 1635 cm^-1, Peak 5 ... 1375 cm^-1, Peak 6 ... 1255 cm^-1. (3a) Ultraviolet absorption spectrum (methanol solution) 203 nm (log ε = 4.4), 215 nm (should
Maximum) and 277 nm (log ε = 4.3)
There is. (4a) Mass spectrum (FABMS, m / z) 1305 (Molecular ion peak, (MH)^-). (5a)¹1 H-NMR spectrum (d₆-DMSO delta
(Ppm)) 7.58 (2H, br, s, cinnamoyl 2 ', 6'H),
7.52 (1H, d, J = 15.8Hz, cinnamoyl γ
H), 7.38 (3H, br, s, cinnamoyl 3 ', 4',
5'H), 6.40 (1H, d, J = 15.8Hz, thinner
Moyle βH), 5.37 (1H, d, J = 10.0Hz, 2
2β-H), 5.33 (1H, br, s, 12-H), 5.
31 (1H, d, J = 10.0Hz, 21α-H), 5.0
6 (1H, br, s, 16-H), 4.82 (1H, d, J =
4.7Hz arabinose anomeric H), 4.70
(1H, d, J = 6.7Hz xylose anomeric
H), 4.39 (1H, br, d, galactose ano
Merrick H), 4.38 (1H, d, J = 7.3Hz group
Chronic acid anomeric H) 3.8-3.2 (sugar origin)
Coming) 3.16 (1H, ABq, 28-Ha), 3.06
(1H, br, d, 3α-H), 2.97 (1H, ABq,
d, 28-Hb), 2.50 (1H, br, S, 18-
H), 2.27 (1H, m, 19-Ha), 2.14 (3
H, S, 21-O-Ac), 1.78 (1H, m, 11-H
a), 1.71 (3H, S, 16-O-Ac), 1.68
(1H, m, 15-Ha), 1.68 (1H, m, 2-H
a) 1.51 (1H, m, 2-Hb), 1.51 (1H,
m, 1-Ha), 1.47 (1H, m, 11-Hb), 1.
42 (1H, m, 7-Ha), 1.39 (1H, m, 6-H)
a) 1.25 (1H, m, 19-Hb), 1.24 (1
H, m, 6-Hb), 1.23 (1H, m, 15-Hb),
1.21 (3H, s, 27-H₃) 1.13 (1H, m, 7
-Hb), 1.00 (3H, s, 30-H₃), 0.92
(3H, s, 23-H₃), 0.82 (3H, s, 25-
H₃), 0.82 (1H, 1-Hb), 0.80 (3H, s,
29-H₃), 0.79 (3H, s, 26-H₃), 0.71
(3H, s, 24-H₃), 0.63 (1H, m, 5α-
H), (6a)¹³C-NMR spectrum (d₆-DMS
O) Shown in Table 1, Table 2 and Table 3. Table 1 shows aglyco
Part of¹³C-NMR spectrum, Table 2 shows acyl group
Minute¹³The C-NMR spectrum and Table 3 show the sugar moieties. ¹³C
-Showed NMR spectrum.

[0007]

[Table 1]

[0008]

[Table 2]

[0009]

[Table 3]

The theasaponin B _{1 of the} present invention is a raw or steamed tea leaf or a tea leaf processed for drinking (such as green tea).
Is extracted with a lower aliphatic alcohol or a hydrous lower aliphatic alcohol, the extract is subjected to various column chromatography, and then separated and purified by high performance liquid chromatography.
Theasaponin B ₁ has an anti-inflammatory action and an anti-allergic action, and is a useful compound as a medicine. According to the present invention, secondly, the following formula (2)

[Chemical 4] A novel desacylsaponin compound represented by (hereinafter referred to as desacylteasaponin B) is provided. The desacyl theasaponin B represented by the above formula (2) has the following physical properties. (1b) Optical rotation [α] _D ²⁵ = + 11 ° (C = 0.8, methanol) (2b) Infrared absorption spectrum (KBr diffuse reflection method) (3b) As shown in FIG. In FIG. 2, peak 1 ····· 3410cm ^-1, peak 2 ····· 2945cm ^-1, a peak 3 · · · · · 1639 cm ^-1, peak 4 · · · · · 1375 cm ^-1, peak 5 1078 cm ^-1 , peak 6 1047 cm ^-1 , (4b) mass spectrum (FAB-MS, m / z) 1115 (molecular ion peak, (M + Na) ⁺ ) (5b) high resolution FAB-MS observed value 1115.5190 (calculated value: 1115.5 against molecular formula C ₅₂ H ₈₄ O ₂₄ Na ⁺ .
250) (6b) ¹ H-NMR spectrum (d ₆ -DMSO) shown in FIG. 3. (7b) ¹³ C-NMR spectrum is shown in Tables 4 and 5. Table 4 shows ¹³ of the aglycon part
C-NMR spectrum and Table 5 show ¹³ C-NM of sugar part.
The R spectrum is shown.

[0011]

[Table 4]

[0012]

[Table 5]

Desacyl theasaponin B of the above formula (2)
Can be easily obtained by hydrolyzing the theasaponin B ₁ of the formula (1). It can also be obtained by hydrolyzing the crude saponin mixture and separating and purifying by HPLC or the like. Hereinafter, the present invention will be described in more detail with reference to Examples.

[0014]

【Example】

Example 1 Powdered tea (Yabukita variety, 20 kg, produced in Uji) was subjected to heat extraction (relux) with methanol (401) three times. The methanol extracts were combined and the solvent was evaporated under reduced pressure to give a methanol extract (2.2 kg). Methanol extract (100 g) was repeatedly purified by silica gel column chromatography [silica gel 2 kg, developing solvent: chloroform-
Methanol-water 10: 3: 1 (lower layer) to 6: 4: 1 (gradient), and 800 g of silica gel, developing solvent: n-butanol-ethyl acetate-water 4: 1: 5 (upper layer).
(Isocratic)], crude saponin mixture (TS-1
Tentatively named 0.64 g) was obtained. This TS-1 (1.0g)
Is dissolved in dimethyl sulfoxide (5 ml) and HP
LC [Cosmosil 5C ₁₈ column (4.6 mm id x 250 mm) Developing solvent: methanol-water-trifluoroacetic acid 500: 5
00: 1, detected at UV254 nm] to separate main peaks (TS-1.G1 to TS-1.G4). Each of the separated solutions was neutralized with pyridine, and the solvent was distilled off under reduced pressure. Furthermore, the main peak TS-1 / G4 (100 mg)
HPLC [Cosmosil 5C ₁₈ column (4.6mm id x25
Separation and purification with a developing solvent: 0.25% ammonium acetate aqueous solution-acetonitrile 3: 2], main peak TS-1
・ I got G41. Since TS-1 / G41 contains ammonium acetate salt, the concentrated solution was analyzed by HPLC [Cosmosil
_{5C 1 8 column (4.6mm id x250mm} ) eluent: water - acetonitrile - isopropylether 75: 25: 1]
Theasaponin B ₁ is isolated after desalting with (27 mg)
did. Theasaponin B1 exhibited the physical properties (1a) to (6a).

Example 2 (1) The crude saponin mixture (TS-1) (640 mg) obtained in the same manner as in Example 1 was added to a 5% KOH aqueous solution (8 m).
1) was added, and the mixture was stirred at room temperature (25 ° C) for 8 hours. The reaction solution was neutralized with a 5% aqueous HCl solution, and the solvent was evaporated under reduced pressure. The residue was subjected to HPLC (Cosmosill 5C ₁₈ column, methanol-water-trifluoroacetic acid = 500: 500:
Separated and purified by 1), desacyl theasaponin B,
(320 mg) was obtained. (2) Also, 5% aqueous KOH solution (0.5 ml) was added to the theasaponin B ₁ (3 mg) obtained in the same manner as in Example 1, and the mixture was stirred at room temperature (25 ° C.) for 3 hours. 5% of reaction liquid
After neutralizing with an aqueous HCl solution, the solvent was distilled off under reduced pressure. The residue was separated and purified by HPLC (Cosmosill 5C ₁₈ column, methanol-water-trifluoroacetic acid = 500: 500: 1), and desacylteasaponin B, (1.5 mg).
Got By both of the above (1) and (2), desacyltea saponin B exhibited the above physical properties (1b) to (7b).

[0016]

INDUSTRIAL APPLICABILITY The novel saponin compound of the present invention can be extracted from tea leaves and has anti-inflammatory and anti-allergic symptoms.

[Brief description of drawings]

FIG. 1 is an infrared absorption spectrum diagram of the novel saponin compound of the present invention.

FIG. 2 is an infrared absorption spectrum diagram of the desacylsaponin compound of the present invention.

FIG. 3 ¹ H—N of desacylsaponin compounds of the present invention
It is an MR spectrum figure.

Continuation of front page (56) References Pharmaceutical Journal, 1992, Vol. 112, No. 1, p. 1-41 Chem. Pharm. Bull. 1980, Vol. 28, No. 1-, p. 296-300 (58) Fields investigated (Int.Cl. ⁷ , DB name) C07J 63/00 C07H 15/256 REGISTRY (STN) CA (STN) CAOLD (STN) JISST file (JOIS)

Claims (2)

(57) [Claims] 1. The following formula (1): A new saponin compound represented by. 2. The following formula (2): A novel desacylsaponin compound represented by: