Odobromoamide, a terminal alkynyl bromide-containing cyclodepsipeptide from the marine cyanobacterium okeania sp.

Article abstract of DOI:10.1246/bcsj.20160417

The bioassay-guided fractionation of the Okinawan marine cyanobacterium Okeania sp. led to the isolation of the novel cyclodepsipeptide odobromoamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute stereochemistry was determined using a variety of different methods, including chemical derivatization and degradation followed by HPLC analysis. In addition, odobromoamide (1) exhibited broad-spectrum cytotoxicity against a human cancer cell line panel.

Full text of DOI:10.1246/bcsj.20160417

Advance Publication Cover Page
Odobromoamide, a Terminal Alkynyl Bromide-Containing Cyclodepsipeptide
from the Marine Cyanobacterium Okeania sp.
Kosuke Sueyoshi, Takafumi Kudo, Aki Yamano, Shimpei Sumimoto, Arihiro Iwasaki,
Kiyotake Suenaga, and Toshiaki Teruya*
Advance Publication on the web January 26, 2017
doi:10.1246/bcsj.20160417
©
2017 The Chemical Society of Japan

Odobromoamide, a Terminal Alkynyl Bromide-Containing Cyclodepsipeptide from
the Marine Cyanobacterium Okeania sp.
1
1
1
2
2
2
Kosuke Sueyoshi, Takafumi Kudo, Aki Yamano, Shimpei Sumimoto, Arihiro Iwasaki, Kiyotake Suenaga, and
1
Toshiaki Teruya*
1
Faculty of Education, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213
2
Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522
E-mail: t-teruya@edu.u-ryukyu.ac.jp
The bioassay-guided fractionation of the Okinawan marine cyanobacterium Okeania sp. led to the isolation of the novel
cyclodepsipeptide odobromoamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute stereochemistry
was determined using a variety of different methods, including chemical derivatization and degradation followed by HPLC analysis. In
addition, odobromoamide (1) exhibited broad-spectrum of cytotoxicity against human cancer cell line panel.
Marine cyanobacteria are well known as prolific
producers of structurally interesting and biologically active
odobromoamide (1) as a colorless oil.
ESIMS analysis of odobromoamide (1) showed a 1:1
doublet ion peaks with m/z values of 767 and 769, indicating
the presence of a bromine atom. The molecular formula of 1
was determined to be C H BrN O by HRESIMS (m/z
1
–3
secondary metabolites.
Furthermore, some of these
4
–6
compounds have potential as therapeutic agents. During the
past 12 years, several structurally unique compounds
containing a halogen atom as part of an unusual alkynyl halide
moiety have been isolated from marine cyanobacteria.
Jamaicamide A is a highly functionalized lipopeptide with
several intriguing structural features, including an acetylenic
3
7
59
4
8
+
1
767.3577 [M+H] , calcd 767.3595). The details of the H and
C NMR spectra of 1 are summarized in Table 1. The H NMR
1
3
1
spectrum of compound 1 revealed the presence of one NH
group (δ 6.26) and two N-methylamide groups (δ 2.91, 2.96).
H
H
7
13
bromide moiety, which was isolated from Lyngbya majuscula.
The C NMR spectrum indicated the presence of six carbonyl
The cyclic depsipeptide veraguamides were isolated from the
marine cyanobacterium cf. Oscillatoria margaritifera. As part
carbons (δ 165.8, 169.7, 170.6, 170.8, 172.1, 173.5). Two of
C
8
the ten degrees of unsaturation in this compound were
accounted for by a terminal alkynyl bromide moiety based on
of our ongoing efforts to identify novel bioactive marine
9
7
cyanobacterial metabolites, we recently isolated odoamide and
its characteristic carbon chemical shifts (δC 79.4, 38.4). The
odobromoamide (1, Figure 1), a cyclodepsipeptide containing a
terminal alkynyl bromide, from the Okinawan marine
cyanobacterium Okeania sp. In this report, we describe the
isolation, structural determination and biological activity of
odobromoamide (1).
remaining two degrees of unsaturation were assigned to two
rings.
Two-dimensional analyses including COSY, HSQC and
HMBC experiments revealed the presence of proline (Pro),
valine
(Val),
N-methylvaline
(N-Me-Val)
and
N-methylisoleucine (N-Me-Ile). COSY correlations between
H-13/H-14, H-14/H-15 and H-14/H-16 suggested the presence
of a valine-like unit. Furthermore, the HSQC spectrum of 1
indicated that H-13 was attached to an oxymethine carbon (δC
77.5). This residue was therefore characterized as
2-hydroxy-3-methylbutanoic acid (Hmba). The sequence of
these amino acids and Hmba was determined by HMBC
analysis, which indicated correlations between H-6/C-2,
H-6/C-7, H-8/C-7, H-8/C-12, H-13/C-12, H-13/C-17,
H-18/C-17, H-23/C-18, H-23/C-24 and H-25/C-24 (Figure 2).
The structure of the remaining C H BrO unit was
Results and Discussion
A large sample of the marine cyanobacterium Okeania sp.
1.2 kg, wet weight) was collected from Odo, Okinawa
Prefecture, Japan, and extracted with methanol. The extract was
filtered and the filtrate was concentrated in vacuo to give a
residue, which was partitioned between EtOAc and H O. The
organic layer was collected and washed sequentially with 90%
aqueous MeOH and n-hexane. The material obtained from the
(
2
9
0% aqueous MeOH portion was fractionated by ODS column
chromatography, followed by reversed-phase HPLC to give
9
11
2
determined as follows. COSY analysis connected the methine
proton at H-30 which showed correlation to the methyl group at
C-37 to the oxymethine at H-31. Furthermore, oxymethine at
H-31 was connected to the methylene protons at H -34, via the
2
two methylene protons at H -32 and H -33. In addition, HMBC
2
2
correlations between H -34/C-35 and H -34/C-36 and the
2
2
characteristic chemical shifts (δC-35 38.4, δC-36 79.4) led to this
unit being identified as
-bromo-3-hydroxy-2-methyloct-7-ynoic acid (Br-Hmoya)
Figure 2).
The connections between the amino or hydroxy acid units
8
(
and Br-Hmoya were determined by HMBC analysis, and the
final degree of unsaturation indicated that odobromoamide (1)
was cyclic. The NH proton of Val showed a cross peak to the

To determine the absolute configurations of its amino acid
components, we hydrolyzed odobromoamide (1) under acidic
conditions and separated the resulting mixture by HPLC to
yield the different amino acid moieties and Hmba. The
stereochemistries of the Pro, Val, N-Me-Val and N-Me-Ile units
in 1 were determined to be L, L, L and L, respectively, following
Table 1. NMR spectra data for odobromoamide (1) in CDCl
3
a)
b)
Unit
No.
δ C
H
δ , mult (J in Hz)
N -Me-Val
1
2
3
4
5
6
7
8
9
9
1
1
1
170.6
64.9
28.3
19.5
19.6
28.7
172.1
57.2
29.5
3.90, d (10.8)
2.27, m
0.89, d (6.6)
0.95, d (7.1)
2.96, s
1
0
their derivatization with Marfey’s reagant and subsequent
analysis by HPLC. The absolute configuration of Hmba was
determined by chiral HLPC analysis following its
Pro
11
derivatization with phenacyl bromide. A comparison of the
retention time of this phenacyl ester with that of an authentic
4.90, dd (8.4, 5.0)
2.26, m
1.76, m
1.98, m
3.79, m
a
b
0
1a
1b
1
2
standards established an L configuration at the stereocenter of
Hmba.
24.9
47.3
The acid hydrolysis of 1 failed to access to Br-Hmoya,
and compound 1 was therefore hydrogenated with Pd/C prior to
being hydrolyzed to remove the bromine atom and reduce the
terminal alkyne functionality to the corresponding alkane. The
hydrogenation product was then hydrolyzed under acidic
conditions, and the resulting mixture was separated by silica
3.57, m
Hmba
12
165.8
77.5
29.7
18.6
18.1
169.7
65.3
34.9
26.5
1
1
1
1
3
4
5
6
4.77, d (8.3)
2.14, m
0.92, d (6.4)
1.01, d (6.4)
gel
-hydroxy-2-methyloctanoic acid (Hmoaa). The chemical shifts
and coupling constants of the protons of the Hmoaa derived
from natural were identical to those of
column
chromatography
to
give
N -Me-Ile
17
3
1
1
2
2
2
2
2
8
9
0a
0b
1
4.14, d (9.5)
1.95, m
1.52, m
1
1
3
syn-3-hydroxy-2-methyloctanoic acid, proving that Hmoaa
adopted a syn configuration. To determine the absolute
configurations of the Hmoaa moiety, 1 was subjected to
methanolysis, resulting in the isolation of fragment 2 (Scheme
1). This product was treated with trimethylsilyldiazomethane to
give the corresponding methyl ester 3, which was reacted with
Mosher’s reagent. The Δδ values of the MTPA esters revealed
1.04, m
11.7
16.3
29.9
173.5
52.8
32.1
17.3
20.3
0.94, t (7.1)
1.02, d (6.3)
2.91, s
2
3
Val
24
2
2
2
2
5
6
7
8
4.65, dd (8.3, 5.6)
1.91, m
1
4
0.83, d (6.8)
0.91, d (6.4)
6.26, d (8.3)
that C-3 existed as the R configuration, which demonstrated
that the absolute configuration of the Hmoaa moiety in 1 was
NH
29
Br-Hmoya
170.8
42.3
76.4
27.5
3
3
3
3
3
3
3
3
3
3
0
1
3.04, m
4.81, m
2.06, m
1.57, m
1.58, m
1.40, m
2.18, m
2a
2b
3a
3b
4
5
6
7
25.0
19.2
79.4
38.4
14.6
1.22, d (7.4)
a) Recorded at 100 MHz. b) Recorded at 400 MHz.
C-29 carbonyl carbon of Br-Hmoya, whereas the oxymethine
proton (H-31) of Br-Hmoya correlated with the C-1 carbonyl
carbon of N-Me-Val. Thus, the gross structure of 1 was
determined as shown in Figure 2.

cytotoxic activity against HeLa S3 cells.
Experimental
General Experimental Pricedures.
Optical rotation
was measured on a JASCO P-1010 polarimeter. UV and IR
spectra were measured on a JASCO V-660 UV visible
spectrophotometer and a JASCO FT/IR-6100 spectrometer,
1
13
respectively. H, C and 2D NMR spectra were recorded on a
Bruker AVANCE 400 MHz NMR spectrometer. The chemical
shifts were reported in relative to the residual solvent signals
(
δ 7.26, δ 77.0) in CDCl . ESIMS data were obtained using a
H C 3
Waters Quattro micro API mass spectrometer, HRESIMS was
performed on a Waters Micromass Q-TOF spectrometer. HPLC
isolation of odobromoamide (1) was conducted on a JASCO
PU-2080 Plus Intelligent HPLC pump and a JASCO UV-2075
Plus Intelligent UV/VIS detector. Cell viability in 96-well
plates was measured using a BioTek ELx800 absorbance
microplate reader.
2
S, 3R (Figure 3). The absolute stereostructure of
odobromoamide (1) was therefore deduced to be 2S, 8S, 13S,
1
8S, 19S, 25S, 30S and 31R, as shown in Figure 1.
The biological activity of odobromoamide (1) was
evaluated using assays for brine shrimp toxicity and in vitro
cytotoxicity against HeLa S3 cells. Compound 1 showed
moderate toxicity against brine shrimp with an LD50 value of
Marine Cyanobacterial Samples.
Samples of the
marine cyanobacterium, Okeania sp. were collected by hand
from the coast of Odo, Okinawa Prefecture, Japan in May 2009.
The cyanobacterium was identified by 16S rRNA sequence
analysis (see Supporting Information).
Extraction and Isolation. Approximately 1.2 kg (wet
weight) of the cyanobacterial samples were extracted with
MeOH (2.0 L). The extract was concentrated, and the residue
1
3.0 μM and exhibited potent cytotoxic activity against HeLa
S3 cells with an IC50 value of 0.31 μM. In addition, a trypan
blue dye exclusion assay revealed that 1 induced cell death in
HeLa cells, and that this activity was suppressed in the
presence of Z-VAD-FMK, an irreversible and cell-permeable
inhibitor of caspases (Figure 4). This result indicated that the
cytotoxicity associated with 1 was dependent on the caspase
family of proteins. Odobromoamide (1) was also evaluated
against a panel of 39 human cancer cell lines (HCC panel) at
the Japanese Foundation for Cancer Research (see Supporting
Information). The average 50% growth inhibition (GI ) value
was partitioned between H O/EtOAc (1:1). The material
2
obtained from the organic layer was further partitioned between
MeOH/H O (90:10) and n-hexane. The aqueous MeOH fraction
2
(
(
3.0 g) was separated by column chromatography on ODS
30.0 g) using 40% aqueous MeOH, 60% aqueous MeOH, 80%
5
0
aqueous MeOH and MeOH. The fraction (976.4 mg) eluted
with 80% aqueous MeOH was subjected to reversed-phase
HPLC [Develosil ODS-HG-5 (20×250 mm), 85% MeOH at 5.0
mL/min, UV detection at 215 nm] to yield odobromoamide (1,
across all of the cells tested was 28 nM.
4
37.4 mg, t =40.0 min). The purity of 1 was determined as
R
>
95% by HPLC analysis.
Odobromoamide (1): colorless oil; [α]D –38.6 (c 1.0,
MeOH); UV (MeOH) λmax (log ε) 202 nm (4.26); IR (neat)
2
6
–
1
1
3
333, 2962, 1646, 1540, 1204, 1096 cm ; For H NMR
1
3
(
400.13 MHz, CDCl ) and C NMR (100.61 MHz, CDCl )
3 3
+
data, see Table 1; HRESIMS m/z [M+H] 767.3577 (calcd for
C H BrN O , 767.3595).
3
7
60
4
8
Absolute Configurations of Amino Acid Residues in 1.
Odobromoamide (1, 1.2 mg) was treated with 5M
HCl (0.5 mL) at 105 °C for 12 h. The hydrolysate was
concentrated to dryness and partitioned between H O and
2
EtOAc. The aqueous layer was subjected to HPLC [Cosmosil
HILIC (4.6×250 mm), MeCN/10 mM AcONH =85:15 at 1.0
mL/min, UV detection at 215 nm] to yield N-Me-Ile, N-Me-Val,
Hmba, Val and Pro. Each amino acid expect for Hmba was
4
Figure 4. Result of the trypan blue dye exclusion assay
of 1. HeLa S3 cells were preincubated (solid column)
or not (open column) with 50 μM of Z-VAD-FMK
and then treated with the indicated concentrations of
added
with
0.1%
solution
of
Nα-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide
(L-FDAA,
1
. After further incubation for 48 h, cell viability was
Marfey’s reagent, 200 μL) in acetone and 0.5M NaHCO (100
3
determined. Values are the mean
quadruplicate determinations.
± SD of
μL) followed by heating at 40 °C for 90 min. After cooling to
room temperature, the reaction mixture was neutralized with
2
M HCl (25 μL) and diluted with MeOH (300 μL). The
solution was subjected to reversed-phase HPLC [Cosmosil
5C18-AR-II (4.6×250 mm), MeOH/20 mM AcONa=60:40
(solvent A) or 50:50 (solvent B) at 1.0 mL/min, UV detection at
340 nm]. The L-FDAA derivatives of standard amino acids
were prepared by the same procedure. The retention times
(min) of the authentic standards were as follows: L-N-Me-Ile
Conclusion
In conclusion, cyclodepsipeptide odobromoamide (1),
which is a novel analog of veraguamides, was isolated from the
Okinawan marine cyanobacterium Okeania sp. The structure of
1
was established by stereoscopic analysis, HPLC analysis and
derivatization reaction. Structurally, 1 consists of a unique C8
alkynoate unit containing a terminal alkynyl bromide, which is
rarely observed in nature. Odobromoamide (1) displayed
(6.6),
L-allo-N-Me-Ile
(6.9),
D-N-Me-Ile
(11.6),
D-allo-N-Me-Ile (12.2), L-N-Me-Val (5.3) and D-N-Me-Val
(8.5) in solvent A, L-Val (6.8), D-Val (18.3), L-Pro (4.9) and

D-Pro (6.5) in solvent B. The retention times and ESIMS
product ions (m/z [M+Na] ) of the L-FDAA derivatives of
N-Me-Ile and N-Me-Val from the hydrolyzate were 6.6 min
J = 6.9 Hz, 3H), 0.99 (m, 1H), 0.95 (d, J = 6.5 Hz, 3H), 0.91 (d,
+
J = 6.8 Hz, 3H), 0.85 (d, J = 6.7 Hz, 3H), 0.84 (t, J = 7.4 Hz,
+
3H); HRESIMS m/z [M+Na]
727.2180 (calcd for
(
420.1) and 5.3 min (406.1) in solvent A, respectively, proving
C H BrF N O Na, 727.2176).
3
2
44
3
2
7
1
the configurations of N-Me-Ile and N-Me-Val were L. The
retention times and ESIMS product ions (m/z [M+Na] ) of the
L-FDAA derivatives of Val and Pro from the hydrolyzate were
6
R-MTPA ester: H NMR (500 MHz, CDCl ) δ 6.29 (d, J =
3
+
8.7 Hz, 1H), 5.28 (q, J = 6.0 Hz, 1H), 5.03 (d, J = 10.4 Hz, 1H),
4.74 (dd, J = 8.6, 7.0 Hz, 1H), 3.69 (s, 3H), 3.07 (s, 3H), 2.54
(quin, J = 6.6 Hz, 1H), 2.08 (td, J = 7.1, 2,6 Hz, 2H), 2.01 (m,
1H), 1.98 (m, 1H), 1.64 (m, 2H), 1.35 (m, 1H), 1.32 (m, 2H),
1.19 (d, J = 7.0 Hz, 3H), 1.02 (m, 1H), 0.96 (d, J = 6.7 Hz, 3H),
0.94 (d, J = 6.9 Hz, 3H), 0.89 (d, J = 6.8 Hz, 3H), 0.85 (t, J =
.8 min (392.1) and 4.9 min (390.1) in solvent B, respectively,
proving the configurations of Val and Pro were L.
Absolute Configuration of Hmba Unit of 1.
The
absolute configuration of the Hmba unit in 1 was determined
by derivatization with HPLC labeling reagent and chiral HPLC
analyses of the derivatives. Hmba from the acid hydrolyzate of
+
7.4 Hz, 3H); HRESIMS m/z [M+Na] 727.2170 (calcd for
C H BrF N O Na, 727.2176).
3
2
44
3
2
7
1
was treated with 80 μL of a phenacyl bromide solution (12
Brine Shrimp Toxicity Assay.
The brine shrimp
mg/mL in acetone) and 80 μL of a triethylamine solution (10
mg/mL in acetone), and the mixture was stirred at 50 °C for 6 h.
The reaction mixture was subjected to chiral HPLC [DAICEL
CHIRALPAK IC (4.6×250 mm), n-hexane/EtOH=90:10 at 1.0
mL/min, UV detection at 254 nm]. The phenacyl esters of
authentic standards were prepared by the same procedure. The
retention times (min) of the authentic standards were L-Hmba
(Altemia salina) toxicity assay was performed using a slight
modification of the original method. The samples were
dissolved in MeOH and transferred to 0.7 cm squares of filter
paper. The squares were dried and added to test vials of
artificial seawater (2.0 mL). Approximately 10 hatched brine
shrimp were transferred to the vials. After 24 h at room
temperature, the brine shrimp were counted and the percentage
of live verses total shrimp was calculated to determine the LD50
values.
(
12.2 min) and D-Hmba (21.2 min). The retention time and
+
ESIMS product ion (m/z [M+Na] ) of Hmba in 1 was 12.2 min
(
259.1), proving the configuration of Hmba was L.
MTT Assay.
The cytotoxicity against human cell
Isolation of Hmoaa Moiety. A solution of 1 (5.4 mg) in
lines HeLa S3 was measured by means of the MTT assay. HeLa
S3 cells were seeded at 4×10 cells/well in 96-well plates and
3
MeOH (1.0 mL) was treated with 10% Pd/C catalyst and stirred
under an atmosphere of hydrogen at room temperature for 24 h.
The reaction mixture was filtered, concentrated in vacuo and
subjected to HPLC [COSMOSIL 5C -AR-II (10×250 mm),
cultured overnight at 37 °C with 5% CO2. Various
concentrations of compound were added and the culture plates
were kept for 72 h. MTT solution (20 μL, 5 mg/mL in DMSO)
was added to each well and the plate was further incubated for
4 h. After the incubation, all remaining supernatant were
removed and DMSO (150 mL) was added to each well to
dissolve the resultant formazan crystal. Absorbance was
measured by using a microplate reader at a wavelength of 540
nm, using 630 nm as the reference wavelength. The IC50 values
were calculated by curve fitting method.
1
8
8
5% MeOH at 4.0 mL/min, UV detection at 215 nm] to yield
the hydrogenation product of 1. The product was treated with
M HCl (0.5 mL) at 105 °C for 24 h. The hydrolysate was
3
concentrated to dryness and partitioned between H O and
2
EtOAc. The EtOAc layer was separated by column
chromatography on silica gel using n-hexane/EtOAc (3:1 to
0
:1) to give Hmoaa.
1
Hmoaa: H NMR (500 MHz, CDCl ) δ 3.95 (m, 1H), 2.63
Trypan Blue Dye Exclusion Assay.
HeLa S3 cells
3
4
(
dq, J = 7.2, 3.6 Hz, 1H), 1.54–1.29 (m, 8H), 1.22 (d, J = 7.2
were seeded at 8×10 cells/well in 24-well plates, cultured
overnight and then preincubated with or without 50 μM
Z-VAD-FMK for 30 min. The cells were then treated with
various concentrations of compound for 48 h. They were then
stained with trypan blue, and the number of stained cells was
counted.
+
Hz, 3H), 0.90 (t, J = 6.9 Hz, 3H); HRESIMS m/z [M+Na]
97.1126 (calcd for C H O Na, 197.1148).
1
9
18
3
Preparation of MTPA Esters.
A solution of 1
(
6.9 mg) in 5% methanolic KOH (0.5 mL) was stirred for 24 h
at room temperature. The reaction mixture was concentrated,
and the residue was partitioned between CH Cl and H O. The
2
2
2
organic layer was subjected to reversed-phase HPLC [Cosmosil
C -AR-II (10×250 mm), 65% MeOH with 0.1% TFA at 4.0
We thank Dr. T. Yamori (Screening Committee of
Anticancer Drugs supported by a Grant-in-Aid for Scientific
Research on Priority Area “Cancer” from The Ministry of
Education, Culture, Sports, Science and Technology, Japan) for
screening in the human cancer cell line panel. This work was
supported in part by a Grant-in-Aid for Young Scientists (B)
(21710237) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan; University of the Ryukyus
Strategic Research Grant.
5
1
8
mL/min, UV detection at 215 nm] to yield compound 2. The
product was treated with trimethylsilyldiazomethane (10 μL) in
benzene/MeOH (2:1, 60 μL), and the mixture was stirred for 2
h at room temperature, to give methyl ester 3. This compound
was divided into two equal portions (0.3 mg each), and one
portion was reacted with R-MTPACl (10 μL) and DMAP (0.5
mg) in pyridine (50 μL), and the mixture was stirred for 20 h at
room temperature. The reaction mixture was concentrated, and
the residue was partitioned between EtOAc/0.1M NaHCO3
Supporting Information
1D and 2D NMR spectra and HCC panel data for
odobromoamide, and gene screening. This material is available
electronically on J-STAGE.
(1:1). The extract obtained from the organic layer was
subjected to reversed-phase HPLC [Cosmosil 5C -AR-II
1
8
(10×250 mm), 85% MeOH at 4.0 mL/min, UV detection at 215
nm] to yield S-MTPA ester. Using the same procedure as
described above, R-MTPA ester was obtained from the other
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S-MTPA ester: H NMR (500 MHz, CDCl ) δ 6.16 (d, J =
3
8
4
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3.
4.
(
1
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Graphical Abstract
<
Title>
Odobromoamide, a Terminal Alkynyl Bromide-Containing Cyclodepsipeptide from the Marine Cyanobacterium Okeania sp.
Authors' names>
Kosuke Sueyoshi, Takafumi Kudo, Aki Yamano, Shimpei Sumimoto, Arihiro Iwasaki, Kiyotake Suenaga, Toshiaki Teruya
Summary>
<
<
Odobromoamide, a novel depsipeptide containing an alkynyl bromide, was isolated from the Okinawan marine cyanobacterium
Okeania sp. The structure was established by stereoscopic analysis, HPLC analysis and synthetic methods. Odobromoamide
displayed cytotoxic activity against HeLa S3 cells and broad-spectrum cytotoxicity against human cancer cell line panel.
<Diagram>