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Abstract
Twelve xanthones were isolated from the hexane extract of the heartwood of Garcinia mangostana from Myanmar. Their structures
were determined using 1D and 2D NMR techniques # 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Garcinia mangostana; Guttiferae; Xanthones; Isolation; Structure determination
1. Introduction
Garcinia mangostana L., from which the mangosteen
fruit is obtained, is commonly encountered in southeast
Asia. Most of its metabolites are xanthones (Bennett and
Lee, 1989) with a-mangostin (1), b-mangostin (2), and gmangostin (3) being the major components. We have
previously isolated a number of known triterpenoids and
xanthones as well as a new biphenyl, 3,40 ,5-dihydroxy30 ,4,5-trimethoxybiphenyl, from the hexane soluble
heartwood constituents of G. mangostana from Myanmar (Nilar and Harrison, 2002). We now report the
isolation of twelve new xanthones, most of which are
the result of side-chain modication of the mangostins.
* Corresponding author.
E-mail address: chmhl@leonis.nus.edu.sg (L.J. Harrison).
0031-9422/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved.
PII: S0031-9422(02)00142-5
542
replaced by signals which could be ascribed to a 2hydroxy-3-methylbut-3-enyl group [H 5.11 (1H, br s,
H-19), 4.90 (1H, br s, H-190 ), 4.31 (1H, dd, J=3.2 and
10.2 Hz, H-17), 3.70 (1H, dd, J=10.2 and 12.8 Hz, H16), 3.54 (1H, dd, J=3.2 and 12.8 Hz, H-16) and 1.96
(3H, s, H3-20); C 148.8 (s, C-18), 109.9 (t, C-19), 77.1
(d, C-17), 33.2 (t, C-16) and 18.2 (q, C-20)]. Proof of the
structure as well as the spectral assignments were
obtained using a combination of HMQC and HMBC
spectroscopy (see Experimental). Compound 6 was
therefore 1-hydroxy-8-(2-hydroxy-3-methylbut-3-enyl)3,6,7-trimethoxy-2-(3-methylbut-2-enyl)-xanthone.
Four other co-metabolites which possessed a 2hydroxy-3-methylbut-3-enyl group were isolated. The
rst was 1,6-dihydroxy-8-(2-hydroxy-3-methylbut-3-enyl)3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone (7). Its
1
H and 13C NMR spectra (see Experimental and
Table 1) were almost identical to those of 6 and it
aorded 6 upon treatment with diazomethane. Since
one of the methoxyl groups of 7 was ortho-disubstituted
(C 61.0), the free hydroxyl group must be at C-3 or C-6.
HMBC spectroscopy showed correlations from the prenyl group methylene protons and the second methoxyl
group to the same aromatic carbon and established that
C-3 was methoxylated. The other correlations were in
agreement with the proposed structure.
Compound 8 was isomeric with 7. Comparison of
their 13C NMR spectra revealed only minor dierences
in the xanthone nucleus resonances, with C-2 being
more shielded in the former and C-8 being more shielded in the latter. Similar behaviour was observed for the
side-chain methylene protons and carbons suggesting
that the positions of the alkyl groups had been interchanged and that 8 was therefore 1,6-dihydroxy-2-(2hydroxy-3-methylbut-3-enyl)-3,7-dimethoxy-8-(3-methylbut-2-enyl)-xanthone. Conrmation of this came from
the results of HMBC spectroscopy (see Experimental).
The 1H and 13C NMR spectra (see Experimental and
Table 1) of the trimethyl ether (9) and the dimethyl
ether (10) were also similar to those of 8. It was apparent that 10 was an isomer of 8 whereas 9 was a methyl
ether of 8. As expected, methylation of either 8 or 10
aorded 9, which was identied as 1 - hydroxy - 2 - (2 hydroxy - 3 - methylbut - 3 - enyl) - 3,6,7 - trimethoxy - 8 - (3 methyl-but-2-enyl)-xanthone since its 1H NMR spectrum
contained a chelated hydroxyl resonance (H 13.78).
Compound 10 was therefore 1,3-dihydroxy-2-(2-hydroxy3-methylbut-3-enyl)-6,7-dimethoxy-8-(3-methylbut-2enyl)-xanthone since its 13C NMR spectrum contained a
resonance (C 61.0) characteristic of an ortho-disubstituted methoxyl. 13C NMR assignments of 9 and 10
were made by comparison with those of 8.
The next two compounds diered only by an Omethyl group. The more polar, (16E)-1,6-dihydroxy-8(3- hydroxy- 3 - methylbut- 1 - enyl) - 3,7 - dimethoxy - 2 - (3 methylbut-2-enyl)-xanthone (11) was readily converted to
543
544
Table 1
13
C NMR (125 MHz) spectral data of xanthones 4, 615, 1922
C No.
4a
6a
7b
8b
9a
10a
11b
12a
13a
14a
15a
19a
20a
21a
22a
1
2
3
4
4a
5
6
7
8
8a
9
9a
10a
11
12
13
14
15
16
17
18
19
20
3-OMe
6-OMe
7-OMe
156.9
112.1
159.3
89.6
156.0
98.4
158.6
144.1
137.5
111.4
183.8
104.7
153.4
104.5
144.1
26.3
123.1
132.1
25.9
18.2
159.7
111.9
164.0
88.9
155.4
98.9
158.2
144.9
134.4
112.9
183.0
104.0
155.4
21.4
122.2
131.9
25.8
17.8
33.2
77.1
148.8
109.9
18.2
55.9
56.1
60.9
160.5
111.9
164.7
89.9
156.2
103.2
157.4
145.7
134.8
112.2
183.0
104.2
156.2
21.9
123.2
131.5
25.8
17.8
30.0
89.4
146.5
112.6
17.9
56.5
161.3
108.5
165.1
89.9
156.5c
102.8
157.7
144.7
138.1
112.0
182.9
104.0
156.2c
24.9
88.1
146.0
112.9
18.3
26.9
124.7
131.5
25.9
17.3
56.5
160.6
108.8
163.7
89.0
155.6c
98.3
158.3
144.2
137.5
112.1
182.1
104.0
155.5c
26.2
75.9
147.8
110.0
18.2
29.1
123.1
132.0
25.9
18.2
56.0d
56.1d
61.0
161.3
107.7
163.2
94.3
155.5
98.4
158.1
144.0
137.3
111.9
182.1
103.5
155.5
28.3
77.6
146.8
110.4
18.6
26.2
123.3
131.8
25.9
18.2
160.3
112.0
164.7
90.0
156.3c
103.1
158.0
144.1
133.2
112.1
182.7
104.2
155.8c
21.9
123.4
131.5
25.9
17.8
124.7
139.5
82.3
25.1
25.1
56.6
159.6
112.1
163.9
89.0
155.5c
99.0
158.8
143.5
132.4
112.7
181.7
104.0
154.9c
21.4
122.0
131.9
25.8
17.8
124.3
137.6
82.1
25.5
25.5
55.9d
56.3d
60.5
158.1
107.6
166.3
88.3
155.8c
101.6
157.2
142.7
137.8
112.2
182.2
104.2
154.6c
26.9
91.8
72.0
25.9
25.9
26.6
123.2
132.2
23.9
18.2
158.1
107.6
166.2
88.1
157.1c
98.3
158.1
144.1
137.2
111.9
182.2
104.4
155.5c
26.9
91.8
72.0
23.9
25.9
26.2
123.2
131.9
25.9
18.2
158.2
107.2
164.4
88.2
157.3c
98.3
158.2
144.1
137.2
111.9
182.2
104.3
155.5c
30.7
88.2
143.3
112.6
17.0
23.9
123.2
131.9
25.9
18.2
159.4
111.8
163.9
89.6
152.6c
102.5
156.3
144.4
104.6
113.6
179.9
103.4
152.4c
21.4
122.2
131.9
25.8
17.8
159.4
111.8
163.8
89.5
155.4c
99.4
156.2
146.7
104.7
113.6
179.8
103.5
152.3c
21.4
122.2
131.9
25.8
17.8
55.9d
62.1
56.1
61.0
56.1
61.0
55.9d
56.5d
56.4d
159.5
111.5
163.6
89.1
155.3c
102.6
155.4
143.9
129.7
112.2
181.4
103.6
154.7c
21.3
122.3
131.6
25.8
17.8
37.4
199.7
144.8
124.0
18.0
55.8
159.7
111.6
163.6
88.8
155.2c
99.1
158.0
144.8
130.4
112.2
181.5
103.8
155.4c
21.3
122.3
131.7
25.8
17.8
37.0
199.2
144.9
123.5
18.0
55.8
56.1
61.4
a
b
c
d
56.1
61.0
61.0
61.3
56.0
61.0
60.5
56.6d
62.2
CDC13.
In (CD3)2CO.
Interchangeable within a column.
Interchangeable within a column.
545
3. Experimental
Mps: uncorr. [a]D: CHCl3. IR: CHCl3 unless otherwise specied. UV: EtOH. EIMS: 70 eV. CC: silica gel
(Baker, 40 mm); C18 (Bakerbond, 40 mm). GPC: Sephadex
LH-20 (CHCl3MeOH 1:1 as eluant). HPLC: Lichrosorb silica, C-18 or DIOL, 10 mm, 4.5250 mm or
9.0250 mm, RI detection. NMR spectroscopy: 500
(1H) and 125 MHz (13C) in CDCl3 (unless specied
otherwise) relative to TMS at 0.0.
Isolation. The heartwood of Garcinia mangostana was
collected in Yangon, Myanmar in 1995. The plant
material was identied by the Singapore Botanic Gardens and a voucher specimen (LJH067) is retained in
the National University of Singapore herbarium. After
air-drying and grinding, the wood (1.3 kg) was extracted
exhaustively with hot hexane (5 l). Concentration of the
solution aorded a crude extract (23 g), which was subjected to column chromatography (silica, EtOAchexane
gradient). A combination of gel permeation chromatography and HPLC of the resulting frs. aorded the following compounds in order of increasing polarity:
garciniafuran (4) (5 mg), 1 - hydroxy - 8 - (2 - hydroxy - 3 methylbut-3-enyl)-3,6,7-trimethoxy-2-(3-methylbut-2enyl) - xanthone (6) (2.3 mg), (16E) - 1 - hydroxy - 8 - (3 hydroxy - 3 - methylbut - 1 - enyl) - 3,6,7 - trimethoxy - 2 - (3 methylbut-2-enyl)-xanthone (12) (2 mg) and 1-hydroxy2-(2-hydroxy-3-methylbut-3-enyl)-3,6,7-trimethoxy-8-(3methylbut-2-enyl)-xanthone (9) (2 mg), b-mangostin (2)
(54 mg), 1,6-dihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)3,7-dimethoxy-8-(3-methylbut-2-enyl)-xanthone (8) (11
mg), (16E)-1,6-dihydroxy-8-(3-hydroxy-3-methylbut-1enyl)-3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone
(11) (10 mg) and 1,6-dihydroxy-8-(2-hydroxy-3-methylbut-3-enyl)-3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone (7) (11 mg), 1,3 - dihydroxy - 2 - (2 - hydroxy - 3 methylbut-3-enyl)-6,7-dimethoxy-8-(3-methylbut-2-enyl)xanthone (10) (7 mg) and mangostanin (13) (30 mg), 6O-methylmangostanin (14) (4 mg), 1,6 -dihydroxy -3,7 dimethoxy-2-(3-methylbut-2-enyl)-xanthone (19) (8 mg)
and 1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)8-(2-oxo-3-methylbut-3-enyl)-xanthone (21) (7 mg).
546
547
m/z (rel. int.): 454 [M]+(2), 452 (3), 436 (38), 411 (25), 395
(94), 365 (20), 357 (42), 349 (37), 341 (25), 339 (61), 325
(19), 202 (19), 95 (21), 73 (18), 69 (26), 55 (44), 43 (100).
HREIMS m/z 454.2005 (C26H30O7 requires m/z
454.1992). 1H NMR: 12.88 (1H, s, 1-OH), 9.77 (1H, s, 18OH), 7.20 (1H, d, J=16.5 Hz, H-16), 6.81 (1H, s, H-5),
6.37 (1H, s, H-4), 5.97 (1H, d, J=16.5 Hz, H-17), 5.21
(1H, t sept, J=7.0 and 1.4 Hz, H-12), 3.99 (3H, s, 6-OMe),
3.92 (3H, s, 3-OMe), 3.70 (3H, s, 7-OMe), 3.35 (2H, br d,
J=7.0 Hz, H2-11), 1.79 (3H, s, H3-15), 1.68 (3H, br s, H314), 1.48 (6H, s, H3-19 and H3-20). 13C NMR: see Table 1.
3.9. Mangostanin (13)
Yellow solid, mp 215217 C. [a]D 0.7 (c 1.17 in
CHCl3). UV lmax nm (log "): 246 (4.57), 318 (4.37), 350
(4.11). IR max cm1: 3506 (OH), 1661 (CO), 1611 (Ar),
1463, 1283, 1171. EIMS m/z (rel. int.): 426 [M]+ (52), 411
(41), 383 (100), 365 (14), 339 (14), 323 (13), 311 (19), 296
(11), 283 (5), 212 (5), 170 (4), 127 (4), 108 (2), 53 (1). HR
EIMS m/z 426.1682 (C24H26O7 requires m/z 426.1679). 1H
NMR: 13.57 (s, exchangeable with D2O, 1-OH), 6.83 (s,
H-5), 6.41 (br s, exchangeable with D2O, 13-OH), 6.28 (s,
H-4), 5.27 (t sept, J=6.3, 1.4 Hz, H-17), 4.77 (dd, J=8.1,
9.4 Hz, H-12), 4.09 (br d, J=6.3 Hz, H2-16), 3.81 (s, 7OMe), 3.19 (dd, J=9.4, 15.4 Hz, H-11), 3.10 (dd, J=8.1,
15.4 Hz, H-11), 1.83 (s, H3-20), 1.70 (br s, H3-19), 1.36
(s, H3-15), 1.24 (s, H3-14). 13C NMR: see Table 1.
3.10. 6-O-Methylmangostanin (14)
Pale yellow gum. [a]D +14.0 (c 0.43 in CHCl3). UV
lmax nm (log "): 248 (4.30), 314 (4.14), 348 (3.66). IR
max cm1: 1662 (CO), 1608 (Ar), 1460, 1427, 1278,
1102. EIMS m/z (rel. int.): 440 [M]+ (31), 425 (18), 407
(10), 397 (100), 379 (22), 337 (23), 119 (10), 69 (11), 58 (10),
43 (38). HREIMS m/z 440.1842 (C25H28O7 requires m/z
440.1835). 1H NMR: 13.64 (1H, s, 1-OH), 6.76 (1H, s, H5), 6.28 (1H, s, H-4), 5.25 (1H, t sept, J=6.6 and 1.3 Hz,
H-17), 4.77 (1H, dd, J=8.1 and 9.4 Hz, H-12), 4.13 (2H,
br d, J=6.6 Hz, H2-16), 3.96 (3H, s, 6-OMe), 3.79 (3H, s,
7-OMe), 3.19 (1H, dd, J=9.4 and 15.4 Hz, H2-11), 3.10
(1H, dd, J=8.1 and 15.4 Hz, H2-11), 1.85 (3H, s, H3-20),
1.68 (3H, br s, H3-19), 1.35 (3H, s, H3-15), 1.24 (3H, s, H314). 13C NMR: see Table 1. This compound was identical
to the product of methylation of 13 with CH2N2.
3.11. Dehydration of 6-O-Methylmangostanin (14)
To a stirred, chilled (10 C) soln of the alcohol (14)
(10 mg) in dry pyridine (2 ml) was added freshly distilled
SOCl2 (0.5 ml). After the reaction was complete (by
TLC), the soln was poured into ice-cold aq. NaHCO3
and extracted with CHCl3. CC of the crude product
(silica gel, 3% EtOAchexane) gave (15) (7 mg). Brown
gum. UV lmax nm (log "): 248 (4.08), 314 (3.93), 352
548
H-5), 6.21 (s, H-4), 6.19 (br s, H-19), 5.86 (br s, H-19),
5.20 (t sept, J=7.1, 1.4 Hz, H-12), 4.67 (s, H2-16), 3.85
(s, 3-OMe), 3.75 (s, 7-OMe), 3.31 (br d, J=7.1 Hz, H211), 2.01 (s, H3-20), 1.78 (s, H3-15), 1.67 (br s, H3-14).
NOE: 7-OMe [H2-16]. 13C NMR: see Table 1. HMBC:
H-4 [C-2, C-3, C-4a, C-9a]; H-5 [C-6, C-7, C-8a, C-10a];
H2-11 [C-2, C-12, C-13]; [C-12, C-13, C-15]; H3-15 [C12, C-13, C-14]; H2-16 [C-7, C-8, C-8a, C-17]; H2-19 [C17, C-20]; H3-20 [C-17, C-18, C-19]; 1-OH [C-1, C-2, C9a]; 3-OMe [C-3]; 7-OMe [C-7].
Acknowledgements
We thank the National University of Singapore for
nancial support and the award of a postgraduate
scholarship to Nilar.
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