JPS6064996A - Tannin - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R<5>, R<6>, R<7> are H, methyl, galloyl group of formula II), formula III (G is galloyl group), formula IV (R<11>, R<12>, R13, R<14> are H, galloyl group; R<10> is H, OH) and formula V (R<20>, R<21> are H, methyl). EXAMPLE:1,2,3-Tri-O-galloylglucose. USE:Metabolism regulator. PREPARATION:For example, seeds of HISHI (Trapa japonica Flerov.) is extracted with aqueous acetone, afte actone is distilled off, the remaining aqueous solution is extracted with ethyl acetate about 10 times to collect the ethyl acetate extract, which is subjected to column chromatography filled with Sephadex LH-20 with solvents of ethanol and 80% aqueous methanol to give galloylglucose of formula I .

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to tannins useful as pharmaceuticals and methods for producing the same.

Tannins are widely distributed in the plant kingdom, and have been widely used as an astringent due to their astringent properties, and as a tanning agent to transform hides into leather. Tannin has a molecular weight of 600
-2000 has a complex structure, and this combined with the difficulty of isolation and purification has delayed research.

On the other hand, useful medicinal effects have been known based on enzyme inhibitory effects such as tannins, and the present inventors have isolated and obtained novel tannins from many plants to demonstrate their pharmacological effects. We tested it and found that it has an enzyme inhibitory effect. It has been found that the compounds according to the present invention reduce the activity of enzyme proteins in the body by binding to them.

Compounds according to the invention are useful as metabolic regulators.

All of the compounds according to the present invention, except for Eugeniin, are new compounds that have not been described in any literature.

A more detailed explanation of Eugeniin is as follows. That is, according to the present invention, raw water chestnut peel 1
．． As much as 7.7 g of Eugeniin can be obtained from 6 kg (equivalent to 500 g of dry matter). In the existing method, 560mg of Eug from 500g of crude drug cloves
It has been revealed that eniin can be obtained, but the present invention utilizes water chestnut peel, the remaining pericarp waste from which starch has been removed, to obtain Eniin at about 14 times the yield.
It is possible to obtain ugeniin.

The compounds according to the present invention include Yang Mei Peel, Cinnamon Peel, Cinnamon Peel, Citrus Peel,
It can be easily obtained from plants such as rhombuses, oak bark, and lingonberry leaves by known methods such as extraction with acetone, ethyl acetate:water partitioning, and column chromatography.

The extraction method according to the present invention can be summarized as follows, for example.

(See next page) Examples will be described in detail below.

Example 1 Extract 1.6 kg of rhombus seeds with 80% aqueous acetone 1β, distill off the acetone, and add 200 ml of the aqueous solution to ethyl acetate! Separate the solution about 10 times, collect the ethyl acetate soluble part, and add 5ephads.
Column chromatography using ex LH-20 with solvent ethanol and 80% aqueous methanol! '3ft 1'? J'
When JIJ was carried out, 1.8 g of the following substance was found in 147 pieces. Yellow needles.

m, p, 24B-250°c (decomp, )
+ [α)? + 106.2° (c = 0.83.
Acetone)Anal Calcd for C
44H30o, 7・21120: C, 49, 71:
H, 3, 46 1 round: C, 49, 46: If, 3.7
8Ill-NMR (Acetone-d6) δ near,
16.7.12.7.06 (each 211.s, g
alloy If ), 6.36 (III, d
, J=811z.

CI-II), 6.02 (ill, t, J =
1011Z, C3-II), 5.80(11(,t
, J=1011z, C4-II), 5.76 (I
II, t, J=1011z, C2-11), 5.1
6 (111, dd, J=6,1011z, Cs −
11A), 4.18 (Ill, d, J=1011
z, Cs-IIB), 4.40 (Ill.

5exteL J=6,1011z, CH; -1ri
+ 4.66 (IH, s, CI"-II) + 6.
82 (ill, s, C2'-H) + 6.40 (
IH, s, 03''-11) ++3 C-NMR (8cetone-dG) δ:, 168.2, 166
．． 3. 166.0°164.8. 164.1 (-
COO-), 119.6. 119.4, 118.9 (
galloyl G-1), IO2,9(galloyl
yl G-2, C-6).

145.7 (galloyl C-3, C-5),
139.7. '139.3 (galloyl C-4)
, 112.3 (C-1') , 122.8 (C
-2'), 107.6 (C-3'), 141.
9 (C-4').

135.5 (C-5'), 150.8 (C-6
'), 42.7 (C-1'').

119.4 (C-2″), 131.0 (C-3
"'), 191.8 (C-4"), 96.4
(C-5”), 91.1 (Cs”).

92.6 (C-1), 70.9 (C-2), 72
．． 7 (C-3).

68.9 (C-4), 73.2 (C-5), 6
5.7 (C-6) Trapain Example 2 A thickness of 30 mg of the following Ga1loyl glucose ti was prepared from 1.6 kg of rhombuses in the same manner as in Example 1.

Colorless amorphous powder [α) Tongue + 48.58 (C = 1.0
0゜acetone), III-NMR (acetone-de) δ:6.98-7.20 (61Lgall
oil-If), 6.12 (11Ld, J=811
z, Ct-If), 5.62 (11Lt, J-8
+Iz, Ca-If).

5.42 (11Lt, J=811z, C2-1f)
, 4.02 (III, br, t.

J-811z, C4-If), 13C-NMR
(Acetone-dG) δ: 165.9.165.4.1
64.6 (s', -ゝC=0) 145.5゜14
5.7 (s, Miss), 121.0.120.4.11
9.8 (138,8,138,6(s, 4),
93.2 (d, Ct).

78,. 3 (d, C3), 76.1' (d, Cs
), 71.6 (d.

C2), 69.1 (d, C4), 61.7
(t, C6).

1+ 2+ 3-Tri-0-galloylgluc
Methyl-2+3+6 was obtained from ose Shichien by the same method.
-Tri-O-galloyl glucose (colorless amorphous powder) is obtained. Yield 0.001% [αV+84.3° (c = LOacetone)
PMR (acetone-dG) ppm: 3.4
4 (3H, s.

-0C113), 3.90-3.96 (211, m
,C4-11,C! ;-11).

4.56 (2H, m, Ce-2H), 4.76
(11Ld, J=8jlz.

Ct-II), 5.16 (Ill, d, d, C2
-It), 5.50 (11Lm, C3-II),
7.02. 7.19 (611, each s, ga
lloyl-1t) CMR (acetone-dG)
ppm: 56.8 (a, 0C) 13), 64
．． 0 (t, cG), 69.6 (d, C4),
72.5 (d.

C2), 74.8 (d, Cs), 76.1 (
d, C3).

102.2 (d, C1), 109.7 (d, -g
alloy-C2,6) 120.4. 120.5+
120.9 (each s, galloyl-CI
) 138.8 (s, galloyl-C4), 1
45.7. 145.5 (each s, galloy
l-C3ts), 165.8. 166.6+1
66.9 (each s, -COO-).

Similarly from Jiyu, 2.3.4+6'Tetra-0-ga
lloylglucose (yield 0.01%) is obtained. Yellowish-brown amorphous powder.

PMR (acetone dG) ppm: 4.1
4-4.70 (311,m+Cs-H,cG-)
1) + 5.16 (dd, J=1011z, 411
z, ct-C2-If) + 5.55 (t+ J
-1011z, α, C4-II) +5.62 (d,
J-4IIz, α, CI-II), 5.80
(t, J=10112, β-C3-H), 6.
12 (t, J”1011z, α-(:3-II)
, 6.95-7.20. (811, m, gallo
yl-1f).

Similarly, from elm, 2,3.4-tri-0-gallo
yl 81ucose (yield o, ooi%) is obtained. Colorless needle crystals (water of crystallization) m, p, 183-184°C.

PMR (acet+one dG) ppm: 3.5
0-4', 1B (m, α, β-Cs e -tl)
, 4.98-6.15 (m, α, β-CI 234
-It), 6.98-7.19 (m, gal
oil-11), a.

PMR not analyzed due to m1xture of β.

Similarly, Methyl 3,4.6-tri-0 from Jiyu
-galloylglucose (yield, rate 0.004
%). Yellowish-brown amorphous powder.

[z+F-'-5z, 7. (.-0,6, aceto
ne ) PMR (aceto'ne de) ppm
3.52 (311, S, OCI+3), 3.69
(IH, t, J-811z, C2-H), 4.
15 (LH, m.

C6-If), 4.40 (2H,m,CB-I
f), 4.58 (11Ld.

J=811z, C11I), 5.37 (11L
t, J = 911z, C4-'II), 5.5
6 (IH, t, J = 911z, C3-It),
7.04°7.07,7.20 (each 2H,
s, ga'1loyl-11).

Mefbyl 2+3+4+6-tet from Jielm as well
ra-0-galloylglucose (yield 0.
006%). Colorless amorphous powder.

[αlD+33.8° (c = 0.94, aceto
ne) PMR (acetone de) ppm
3.50 (3B, s, 0CI13), 4.24-4
．． 70 (311, m, Cs, s-II), 4.
95 (11Ld,, T-811z, CI-H),
5.35 (LH, t, J=811z, l':2-H)
, 5.55 (IH, t, J=911z, C4-II
), 5.85 (IH, t, J = 9H2, C3-II
), 6.96. 7.07, 7.09+ 7.23
(each 211.s, galloyl)
.

Example 3 Extract 6.3 kg of the skin of Japanese oak with aqueous acetone 51, separate the liquid with ethyl acetate lβ, collect the ethyl acetate soluble part,
After repeated column chromatography separation using 5ephadex LH-20, the following Ga1loyl 5a was obtained.
Lidrosides were obtained.

1. Yellowish brown amorphous powder (yield 0.001%) [αll
o +4.5 (c = 0.5. MeOH) PMR (
CD300) ppm: 2.83 (21Lt, J=
711z.

-CI+2-ψ), 3.3-4.2 (glib
, C2+ 41 s +e -If) , 14.4
2 (ill, d, J=8tlz, anom II)
, 5.12 (ltl, t, J=10Hz, glu
, C3-H) , '6.68 (2H, d, J=81
12, C3+ s -II) + 7.50 (21
1, d, J=811z, C2.

6-It), 7.12 (2H,s,,gal,I
l).

CMR (CD300) ppm: 76.2 (t,
-CI+2- φ)112.3 (t, glu, Ce
)', 69.7 (d, glu, C4).

72, ID, -C112-φ), 73.4 (d,
glu, C2).

77.6 (d, glu, Cs), 79.0 (d
, 'glu, C3).

104.0 (d, C+), 110.2 (gal
, C2, e).

115.9 ('d, C3, s), 121.5
(s, gal, self).

130.5 (s, C4) + 130.7 (S, C
2,e).

139.4 (s, gal, C4), 146.0 (
s, gal, C3.

s), 153.6 (S, C4), 167.9
(s-COO-)2, pale yellow needles (yield 0.5%) ip, 116-117°C (αlo+15.1° (C= 0.9+ aceto
ne) PMR (acetone-ds) ppm
: 27.8 (211,t, J=7tlz, -C1
12-φ), 3.30-4.10 (glu, C
2, 3.

41s -If) + 4.40 (11LLJ=81
1z+anom, ll) 14.41 (IN, d, d
, J=12,411z, glu, c6 , +1) , 4
．． 58 (IH, d, d, J=12,211z, glu
, cs-II), 6.72 <21Ld, J=8H
z, C3, 6-If), 7.03 (211, d, J
=8Hz, C2.

s-II), 7.17 (211, s, gal, l
I).

CMR (acetone-de) ppm: 3
5.7 (t, -C112-φ), 64.4 (t,
glu, Ce), 71. OD, -0CI+2')
.

71.4 (d, glu, Cr), 109.6 (
d, gal, C2.

6), 115.6 (+i, C3,s),”
'121.0 (s, gal.

from), 129.7 (s, from), 130.3
(d, C2.

6) 1 145.6 (s4a1.C3,s)+1
55.9 (s.

C4), 166.9 (s, -COO-).

3. Colorless amorphous powder (yield 0.002%) [α]D +
20.9° (c = 0.3+ acetone)P
MR (acetone-ds) l)I)m:
2.80 (211,t, J=711z.

-CI+2-φ), 3.32-4.04 (glu
, C3,4,6-It), 4.20 (ill,
dd, J=12.411z, glu, Cs-II)
.

4.42 (III, dd, J = 12,3 tlz, g
lu, ce -0), 4.50 (1tLd, J=8
11z, anom, Il) 15.13 (IILt,
J=81+z.

glu, C2-H), 6.71 (ill, d,
, T-8) 1z, C2, 5-If) , 7.04
(21Ld, J=811z, C2, s -If),
7.14°7.16 (eacb 211.s, ga
l,lI).

CMR (acetone-ds) ppm: 35
．． 7 ←CH2φ).

63.5 (glu, Cs),'(71,5gl
u, C4), 72.0 (0CR2), 72.5
(glu, C2) 74.5 (glu, Cs
).

75.2 (glu, C2), 103.6 (gl
u, CI), 109.7°109.9 (gal
, C2, s), 115.7 (self, 5).

120.5. 120.8 (gal, C1), 12
6.9 (Ct).

130.4 (C2, e), 145.7 (gal, C
3,6x2'), 155.9 (C4), 166
．． 5,166.8 (-COO-).

4. Colorless amorphous powder (yield 0.002%) [α1. -2
1.0° (c = 0.3Lacetone) PMR (
acetone-ds) fll) Tn: 2.9
1 (211,t, J=7Hz.

-CI+2φ), 3.10-4.12 (glu,
C2, 3, 4.

6-H), 4.36 (Ill, dd, J=12
, 611z, glu, cs-II) + 4.40 (
IH+ d, J = 8Hz, anom, H) + 4.
58 (Hl, dd.

J = 12,211z, glu, ce-tl),
7.07 (2i1.d, J=8Hz.

C3, s - If), 7.19 (28, d, J=
811z, C2, s-tl), 7.19.7.2
6 (each 211.s, gal, H).

CMR (acetone-CIS) ppm:
36.0 (-Cl12φ)164.5 (glu,
CB), 71.0 (glu, C4, -0C112
−).

74.2 (glu, C2), 74.5 (glu,
Cs), 77.2(glu, C3), 1[13,
6 (glu, CI), 109.6°110.0 (
glu, C2, e), 120.3. 121.0
(gal.

CI ) 121.1' (C3,s), 130.4 (C
2, CG), 136.8 (CI), 138.7, 1
39.3 (glu, ct).

145.7. 145.8 (gal, C3, s)
, 150.1 (C4) 165.7. 167.0 (
-COO-).

5. Pale yellow amorphous powder (yield o, ooj%) [α1D-3
6,2° (C=Q, 24.acetone) PMR (
acetone-d6) ppm: 2.75
(2tLt, J=8Hz.

-CI2 φ), 3.2-4.08 (glu, C2
, 3+ 41s -) 1) , 4.39. 4.58
(each IH, dd, J=12.12Hz.

glu, CB -11) + 4.40 (11,d,
J=81 (z+anom, H).

6.53 (IH, dd, J=8,211z, Cs i
f), 6.71' (ill, d, J=8Hz, C6
-11), 6.74 (III, d, J=2Hz, C
2-II) 7.17 (211, s, gal, ll)
.

RI R2R3R4R6 IHHI G H 2HHHHG aHHGHG 4HG HHG 5011 HHHG Example 4 The following substance was obtained from a ground elm in the same manner as in Example 3.

Yellow-brown crystals. mp, 209-210°C (yield 0.00
2%) (lD+38.8° (1120-aceton
e+ 8: 2+ C=0.79) 8 na1. calcd, for C271 (24o18
° H20C49,56: H4,00 Found C49,47: H4,05)'Mll
(acetone-(Ic) ppm: 5.3C1
(d, J = 1311z.

(1'-(:3-II Or β-C3-1f),
5.5 (L 5.52 (each s.

α-Cl-If, β-C1-II), 5.64
(d, J =811z.

α-C3-II or β-C3-If), 7.0
4-7.40 (611, m.

Galloyl, H).

CMli (CD3 oD) ppm: 65.0
(α-Ce), 66.8 (β-Ce), 67
．． 0 (α-C5), 67.2 (β-C5).

73.6 (α-C3), 75.6 (β-c, )
, 78.9 (α--C2), 79.3 (β-
C2), 81.5 (α, β-C4), 98.4 (
α-CI), 103.1 (β-cl), 11
0.1 (galloyl-C2+CG), 120
．． 2. 120.5. 120.7゜121.0 (g
alloy-CI), 139.7 (gallo
yl-C4), 146.1 (galloyl-C
3”', Cs), 167.5°167.7.1
68.1 (-COO-).

3-O-Galloyl hamamelitanni
If this product, MeSO4, and 2CO3 are refluxed in acetone for 3 hours, a methylate (colorless amorphous powder) of this product can be obtained with a yield of 60 to 70%.

[α+22.5 (c =0.32. Cl1C13
) Example 5 1.6 kg of rhombus pericarp was extracted with 31 parts of acetone, the acetone was distilled off, and the aqueous solution was partitioned with ethyl acetate (11 parts).

The ethyl acid transition part was subjected to 5 epbadex Lit-20 column chromatography, and Eugeni having the following structural formula was obtained.
In 7.7g was isolated.

Example 6 The following substance was obtained from 2.13 kg of chestnut bark by the same method as above.

■Compd XV hamamclitannin
((No+30.2°(H2O) Yield (0.28%) Colorless needle crystals mp, 148°C PMR (acetone d6) ppm: 5.32
．． 5.38 (18in total, each s,
αC1-8, βC1-H)+ 7.14+ 7.18
(each 2111 S-1 galloyl-It
)■Compd XVl 3+5+2'-tri-0-
galloyl hamame-ose Yield (0,007%) Colorless needle crystals. mp, 210℃
[αlo +29. O° (acetone −)l'
20) PMR (acetone de) I) pm
: 5.20. 5.59 (IIIin tota
l + d+ J=811z+ ca-11)+ 5.
44+ 5.48 (IHin total, s, c
x C1-)1. βC1-11>, 7.12+ 7.
16+ 7.20 (eac, h 21L S, gal
loyl-II) CMR (acetone ds)
ppm: 64.8+ 66.3°66.7.67.
0 (C5-α, β, 02'-α, β), 73.1
(C3-α), 74.9 (C3-α), 78.5 (
C2-α), 78.9 (C4-α, β)'+8
1.1 (C2-β)97,. 9 (CI-α), 10
2.7 (C1-α), 110.0 (C=0) or more

Claims (1)

[Scope of Claims] A compound represented by the following general formula (I represents a hydroxyl group) and the following -(R2°, R2
1 is the same or different and represents hydrogen or methyl. ) A novel tannin selected from the group consisting of the compounds represented by