j nat. prod. 2006, 69, 338-341 cytotoxic xenia diterpenoids from the soft coral xenia umbellata ali...
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Ali A. El-Gamal, Shang-Kwei Wang and Chang-Yih Duh
Department of Marine Biotechnology and Resources,
National Sun Yat-sen University, Kaoshiung, Taiwan,
Republic of China,
Faculty of Pharmacy, Mansoura University, Egypt
&
Department of Microbiology,Kaoshiung Medical University,
Kaoshiung, Taiwan, Republic of China
Abstract
Eleven new diterpenoids, umbellacins
A-G (1-7), 14,15-epoxy-xeniolide H (8), 3-
acetyl-14,15- epoxy-xeniolide H (9), and
umbellacins H and I (11, 12), were isolated
from a methylene chloride-soluble frations
of the soft coral Xenia umbellata. The
structures were elucidated by extensive
spectroscopic analysis, and their cytotoxicity
against selected cancer cells was measured
in vitro.
The soft coral Xenia umbellata was studied
because CH2Cl2 showed significant
cytotoxicity to A549 (human lung
adenocarcinoma), HT-29 (human colon
adenocarcinoma) and P388 (mouse
lymphocytic leukaemia). The aim of this
study will deals with separation, structural
elucidation and biological study of some
cytotoxic xenicane-type diterpenooids
characteristic for xenia umbellata.
A photo of Xenia
A photo of Xenia
Bodies of the soft coral X. umbellata were freeze-dried to give 800 g of a solid
extract with CH2Cl2 (3LX3), conc in vacum
60 g of CH2Cl2 extract
CC, Sil. gel using n-hex. and n-hex. -EtOAc gradient, followed byEtOAc-MeOH, gradient
%of EtOAc/n-Hex
10% 17% 20% 50%40%
%of MeOH/EtOAc
2% 5%
9 8 1 6,10,115 2,4
HPLC (Rp-18), MeOH-H2O (65:35)
HPLC (Rp-18), MeOH-H2O (60:40)
HPLC (Rp-18), MeOH-H2O
3 7
HPLC (Rp-18), MeOH-H2O (60:40)
HPLC (Rp-18), MeOH-H2O (68:32)
HPLC (Rp-18), MeOH-H2O (73:27)
HPLC (Rp-18), MeOH-H2O (82:18)
Sub Fr.. A Sub Fr.. B Sub Fr.. C Sub Fr.. D Sub Fr.. E Sub Fr.. FSub Fr.. G
%of MeOH/H2O
70% 67%
Compounds 2, 4, 5, 6, 10, and 11 exhibited cytotoxicityagainst P-388 lymphocytic leukemia with ED50values of 1.6, 4.2, 3.8, 3.7, 3.4, and 3.6g/m, respectively., none of the isolates were cytotoxic to A549 (human lung adenocarcinoma)and HT-29 (human colon adenocarcinoma) cell lines (IC50> g/mL).
Isolated Xenicane Diterpenoids from Soft Coral Xenia umbellata
OH
H
1
34
5 6
7
9
10
4a
11a
1213
1415
16
17
18
H 11
Umbellacin F (6)
O
MeO
AcO
19
HO
8
Umbellacin G (7)
H
1
4
5 6
7
8
910
11a
1213
14 15
16
17
18
19
H 11
R = H, 14,15-epoxy Xenolide H (8)R= Ac, 3- acetyl 14,15-epoxy- Xenolide H (9)
O
O
RO
OH
O
3
Umbellacin H (10)19
H
1
4
5 6
7
8
910
11a
1213
1415
16
17
18
19
H 11
OH
O
MeO
O
O
3
HO
OH
OH
OH
H
34
5 6
7
89
10
4a
11a
1213
1415
16
17
18
19
H 11
Umbellacin I (11)
O
MeO
AcO
HO
OH
O
OMe
H
1
34
5 6
7
89
10
4a
11a
1213
14 15
16
17
1819
H
MeO
OH
OH
O
OH
O
OH
H
1
3 4
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
Umbellacin C (3)
OHC
OHC
OH
OH
H
1
34
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
Umbellacin A (1)
OH
OH
OH
H
34
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
Umbellacin B (2)
OHO
MeO
AcO
OH
OH
H
34
5 6
7
89
10
4a
11a
1213
1415
16
17
18
19
H 11
Umbellacin E (5)
O
MeO
AcO
HO9
Umbellacin D (4)
OH
H
1
34
4a
11a
1213
1415
16
17
H
O
MeO
AcO
O
H
5
6
7
8
10
11
19
18
HO
OHC
OHC
OH
OH
H
1
34
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
OH
1 313
1214
8
1617
18
1HNMR of Compound 2 (Umbellacin B)
12
17173
OH
H
34
5 6
7
89
10
4a
11a
1213
1415
17
16
18
19
H 11
OHO
MeO
AcO
HO
14
OMe
8
4a 11a13
OAc
16 18
H HCOSY of Compound 2 (Umbellacin B)
HSQC of Compound 2 (Umbellacin B)
OH
H
34
5 6
7
89
10
4a
11a
1213
1415 16
17
18
19
H 11
OHO
MeO
AcO
HO
HSQC of Compound 2 (Umbellacin B)
12 17 3 14OMe
8 4a 11a 13
OAc 16 18
1HNMR of compound 3 (umbellacin C)
O
OH
O
OH
H
1
3 4
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
131210
14
3
3
811a
9
1617
18
1H1 H COSY of Compound 3 (Umbellacin C)
O
OH
O
OH
H
1
3 4
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
13C NMR of Compound 3 (Umbellacin C)
O
OH
O
OH
H
1
3 4
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
114
114
12 10 13
3
158 11a 4a
7
196
9
1617
5 18
HSQC of Compound 3 (Umbellacin C)
O
OH
O
OH
H
1
3 4
5 6
7
89
10
4a
11a
1213
14 15
16
17
18
19
H 11
HMBC of Compound 3 (Umbellacin C)
1H NMR of compound 4 (Umbellacin D)
123
9
OH
H
1
34
4a
11a
1213
1415
16
17
H
O
MeO
AcO
O
H
5
6
7
8
10
11
19
18
HO
8
19
19 4a 11a
OMe
OAc
1617 18
13
Expanded 13C NMR and DEPT Experiment of Compound 4 (Umbellacin D)
8 14 1915 3 OMe 7 11 11a 4a 13
OAc18
9
OH
H
1
34
4a
11a
1213
1415
16
17
H
O
MeO
AcO
O
H
5
6
7
8
10
11
19
18
HO
HSQC of Compound 4 (Umbellacin D)
9
OH
H
1
34
4a
11a
1213
1415
16
17
H
O
MeO
AcO
O
H
5
6
7
8
10
11
19
18
HO
1HNMR of Compound 6 (Umbellacin F)
12 8
193
OMe
14
4a 11a13
OAc
18 1617
OH
H
1
34
5 6
7
9
10
4a
11a
1213
1415
16
17
18
H 11O
MeO
AcO
19
HO
8
13C NMR of compound 6 (Umbellacin F)
OH
H
1
34
5 6
7
9
10
4a
11a
1213
1415
16
17
18
H 11O
MeO
AcO
19
HO
8
1 OAC 11 4 7 12819
15 3 14 11a OMe 9 4a
O
OMe
H
1
34
5 6
7
89
10
4a
11a
1213
14 15
16
17
1819
H
MeO
OH
OH
1HNMR of compound 7 (umbellacin G)
13 12 14
38 19
919
1
OMe OMe
4a
18
1617
1H NMR of Compound 8 (14,15-epoxy xeniolide H)
H
1
4
5 6
7
8
910
11a
1213
14 15
16
17
18
19
H 11
O
O
HO
OH
O
3
12,13 19
3
11a3’
148
94a 5
18
1617
COSY of Compound 8 (14,15-epoxy xeniolide H)
H
1
4
5 6
7
8
910
11a
1213
14 15
16
17
18
19
H 11
O
O
HO
OH
O
3
13 CNMR of Compound 8 (14,15-epoxy xeniolide H)
1 11 13 12 19
4 3 8 14
15 11a 4a
6 18 1617
9 5 107
HMBC of Compound 8 (14,15-epoxy xeniolide H)
NOESY Experiment of Compound 8 (14,15-epoxy xeniolide H)
12,13
19
311a,3’
14
84a9
1H NMR of Compound 9 (3-acetyl 14,15-epoxy xeniolide H)
12,13
19
3
1411a8,4a,10
OAc
X
96
5 10
181617
H
1
4
5 6
7
8
910
11a
1213
14 15
16
17
18
19
H 11
O
O
AcO
OH
O
3
1H 1H COSY of Compound 9 (3-acetyl 14,15-epoxy xeniolide H)
H
1
4
5 6
7
8
910
11a
1213
14 15
16
17
18
19
H 11
O
O
AcO
OH
O
3
Expanded 1H HCOSY of Compound 9 (3-acetyl 14,15-epoxy xeniolide H)
1411a
8 4a
10
965
10
18
16 1
7
13C NMR of Compound 9 (3-acetyl 14,15-epoxy xeniolide H)
1 OAc 11
13
1219
4
38
1415
7
11a4a
6 91618
OAc
10517
HSQC of Compound 9 (3-acetyl 14,15-epoxy xeniolide H)
H
1
4
5 6
7
8
910
11a
1213
14 15
16
17
18
19
H 11
O
O
AcO
OH
O
3
1H NMR of Compound 10 (Umbellacin H)
12 19 19
3
OMe
14 4a11a
8
OAc 18
16 17
19
H
1
4
5 6
7
8
910
11a
1213
1415
16
17
18
19
H 11
OH
O
MeO
O
O
3
HO
OH
1H NMR of Compound 11 (Umbellacin I)
OH
OH
H
34
5 6
7
89
10
4a
11a
1213
1415
16
17
18
19
H 11O
MeO
AcO
HO
OH
12 3
OMe
14
8
4a11a
OAc 16, 17
18
13C NMR of Compound 11 (Umbellacin I)
OH
OH
H
34
5 6
7
89
10
4a
11a
1213
1415
16
17
18
19
H 11O
MeO
AcO
HO
OH
1 OAc 4 12 3 11aOMe 811 15 1
9 4a
7 13,5,18
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