8,17-Epoxybriarane diterpenoids, briaranolides A-J, from an Okinawan gorgonian Briareum sp.

Article abstract of DOI:10.1021/np058037q

Ten new 8,17-epoxybriarane diterpenoids, briaranolides A-J (1-10), were isolated from an Okinawan gorgonian Briareum sp. The structure of the diterpenoids was determined on the basis of spectroscopic analysis, chemical conversions, and X-ray analysis.

Full text of DOI:10.1021/np058037q

1328
J. Nat. Prod. 2005, 68, 1328-1335
8,17-Epoxybriarane Diterpenoids, Briaranolides A-J, from an Okinawan
Gorgonian Briareum sp.
Ayako Hoshino, Hidemichi Mitome, Shinya Tamai, Hiroki Takiyama, and Hiroaki Miyaoka*
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received March 10, 2005
Ten new 8,17-epoxybriarane diterpenoids, briaranolides A-J (1-10), were isolated from an Okinawan
gorgonian Briareum sp. The structure of the diterpenoids was determined on the basis of spectroscopic
analysis, chemical conversions, and X-ray analysis.
A characteristic feature of briarane diterpenoids is the
presence of a highly substituted bicyclo[8.4.0]tetradecane
skeleton.1 More than 300 briarane diterpenoids have pre-
viously been discovered from marine organisms, and the
number is still increasing.2 Some of these possess interest-
ing biological properties such as cytotoxic,3 anti-inflam-
matory,4-6 antiviral,6,7 insecticidal,8 immunomodulation,9
and multidrug resistance reversing activity.10 The chemical
structures of these compounds have mainly been deter-
mined on the basis of spectroscopic analyses. However,
elucidation of functional group stereochemistry remains
problematic due to the flexible configuration of the cyclo-
decane moiety.11 In fact, reports detailing the determina-
tion of an absolute configuration remain sparse.1,5,10,12
During the course of our investigations on the chem-
ical constituents of Okinawan marine invertebrates,13 10
new 8,17-epoxybriarane diterpenoids, briaranolides A-J
(1-10), were isolated from an Okinawan gorgonian Bri-
areum sp. The isolation and structural elucidation of these
new briarane diterpenoids, including determination of
absolute configuration based on chemical conversions and
X-ray analysis, are presented below.
Results and Discussion
The gorgonian specimens of Briareum sp., obtained in
June 2002 from the coral reef of Hatoma Island, Okinawa,
Japan, were extracted with MeOH and then with acetone.
The extracts were combined and then partitioned between
water and EtOAc. The EtOAc-soluble portion was parti-
tioned between 80% aqueous MeOH and n-hexane. Re-
peated chromatographic separation of the 80% aqueous
MeOH-soluble portion led to the purification and subse-
quent characterization of 10 new 8,17-epoxybriaranes,
briaranolides A-J (1-10).
Briaranolide A (1) was found to have the molecular
formula C30H38O13 as determined from high-resolution
ESIMS. The IR spectrum of 1 suggested the presence of a
γ-lactone moiety (1793 cm-1) and ester group (1744 and
1238 cm-1). From 1H and 13C NMR analyses, 1 was found
to possess five acetoxy groups and one γ-lactone moiety
[δH 2.19 (3H, s), 2.09 (3H, s), 2.08 (3H, br s), 2.03 (3H, s),
1.99 (3H, s), δC 170.8 (C), 170.2 (C), 169.3 (C), 169.2 (C),
169.2 (C), 169.0 (C)], in addition to two trisubstituted
olefins [δH 5.47 (1H, br d, J ) 9.2 Hz), 5.46 (1H, br s), δC
140.7 (C), 131.2 (C), 124.3 (CH), 122.0 (CH)] (Tables 1 and
2). 1H and 13C NMR correlations were evident from
inspection of the HMQC spectrum. The planar structure
of 1 was determined essentially from H-1H COSY and
1
HMBC correlations cited in Figure 1. The presence of an
8,17-epoxide was established by the absence of hydroxy
group-derived IR absorptions, the molecular formula, and
the C-8 (δC 71.3) and C-17 (δC 62.1) 13C NMR chemical
shifts.
Briaranolides B (2), C (3), and D (4) were found to have
a molecular formula of C32H42O13, C34H46O13, and C30H40O12,
respectively, based on high-resolution mass spectrometry
and elemental analysis. The IR and NMR spectra (Tables
1 and 2) of 2-4 were similar to those of 1. The functional
groups at C-3 and/or C-4 of 2-4 differed from that of 1, as
determined from 1D and 2D NMR analyses together with
chemical conversions. Briaranolide B (2) has a butyryloxy
group at the C-4 position, while briaranolide D (4) has a
hydroxy group at position C-3 and a butyryloxy group at
position C-4, in lieu of the acetoxy group(s) found in 1.
Briaranolide C (3) was found to have two butyryloxy
groups; the position of one of these was confirmed to be
C-4, while the precise position of the other was difficult to
ascertain by NMR analyses. This problem was solved by
the butyrylation of briaranolide D (4) that yielded briara-
nolide C (3). Similarly, briaranolide B (2) was derived from
briaranolide D (4) by acetylation. The aforementioned
chemical conversions assisted in the unambiguous deter-
mination of the planar structures of 2-4.
* To whom correspondence should be addressed. Tel: +81 426 76 3080.
Fax: +81 426 76 3073. E-mail: miyaokah@ps.toyaku.ac.jp.
10.1021/np058037q CCC: $30.25
© 2005 American Chemical Society and American Society of Pharmacognosy
Published on Web 08/13/2005

Epoxybriarane Diterpenoids from Briareum
Journal of Natural Products, 2005, Vol. 68, No. 9 1329
Table 1. 1H NMR Data for Compounds 1-4 (J in Hz)
no.
1a
2a
3b
4a
2
3
4
6
7
9
10
12
13
5.36
5.08
6.41
5.47
5.81
5.44
3.04
5.46
2.32
2.16
4.78
1.61
1.82
1.47
1.76
2.08
2.03
(d, 3.1)
(br s)
5.38
5.07
6.43
5.46
5.82
5.44
3.04
5.47
2.32
2.14
4.79
1.60
1.81
1.48
1.76
2.07
2.03
(d, 3.0)
(br s)
(d, 3.7)
(br d, 9.2)
(d, 9.2)
(d, 2.2)
(br s)
(br s)
(m)
5.36
5.09
6.43
5.45
5.82
5.42
3.05
5.47
2.28
2.13
4.78
1.64
1.79
1.46
1.75
2.04
(d, 3.3)
(br s)
(d, 3.8)
(d, 9.2)
(d, 9.2)
(d, 2.5)
(br s)
(br s)
(m)
5.43
3.72
6.25
5.38
5.85
5.35
2.88
5.45
2.33
(br s)
(br s)
(br s)
(d, 8.6)
(d, 8.6)
(d, 2.8)
(br s)
(br s)
(m)
(d, 1.0)
(br d, 9.2)
(d, 9.2)
(d, 2.5)
(br s)
(br s)
(m)
(m)
(m)
(m)
14
(dd, 8.5, 6.4)
(br s)
(dd, 8.7, 6.6)
(br s)
(br s)
(s)
(dd, 9.0, 6.6)
(br s)
(br s)
(s)
4.77
1.56
1.88
1.48
1.69
2.07
(t, 7.4)
(br s)
(s)
(s)
(br s)
(s)
15
16
(br s)
(s)
(d, 0.5)
(br s)c
(s)c
18
20
(br s)
(br s)
2-Ac
3-Ac
3-COPr
(s)c
(s)c
(s)c
2′
3′
4′
2.32
1.64
0.97
(dt, 7.4, 1.6)
(quintet, 7.4)
(t, 7.4)
4-Ac
4-COPr
2.09
(s)
2′′
3′′
4′′
2.34
1.67
0.98
2.19
1.99
(t, 7.3)
(quintet, 7.3)
(t, 7.3)
(s)c
2.25
1.66
0.95
2.18
1.97
(t, 7.4)
(quintet, 7.4)
(t, 7.4)
(s)c
2.37
1.70
0.98
2.21
1.99
(m)
(quintet, 7.4)
(t, 7.4)
(s)
(s)
9-Ac
14-Ac
2.19
1.99
(s)c
(s)
(s)
(s)
a 500 MHz in CDCl3. b 400 MHz in CDCl3. c Data are interchangeable in the same column.
Table 2. 13C NMR Data for Compounds 1-4
no.
1a
2a
3b
4a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2-Ac
42.3
72.8
70.7
65.8
140.7
124.3
74.7
71.3
72.6
43.8
131.2
122.0
28.1
73.9
17.6
17.4
62.1
10.2
170.8
22.1
169.3
20.8
169.2
20.5
(C)
42.3
72.7
70.7
65.4
140.9
124.1
74.9
71.3
72.7
43.9
131.2
122.1
28.2
73.8
17.5
17.5
62.2
10.3
170.8
22.1
169.4
20.8
169.3
20.5
(C)
42.3
72.7
70.4
65.6
140.8
124.2
74.8
71.3
72.7
43.9
131.1
122.1
28.1
73.7
17.4
17.5
62.1
10.2
170.8
22.0
169.2
20.8
(C)
42.2
72.7
71.7
66.2
(C)
(CH)
(CH)
(CH)
(C)
(CH)
(CH)
(CH)
(C)
(CH)
(CH)
(CH)
(C)
(CH)
(CH)
(CH)
(C)
141.1
123.5
75.2
71.6
72.7
43.8
131.0
122.4
28.2
74.5
17.3
16.9
62.2
10.2
170.8
22.6
169.5
21.0
(CH)
(CH)
(C)
(CH)
(CH)
(C)
(CH)
(CH2)
(CH)
(CH3)
(CH3)
(C)
(CH)
(CH)
(C)
(CH)
(CH)
(C)
(CH)
(CH2)
(CH)
(CH3)
(CH3)
(C)
(CH)
(CH)
(C)
(CH)
(CH)
(C)
(CH)
(CH2)
(CH)
(CH3)
(CH3)
(C)
(CH)
(CH)
(C)
(CH)
(CH)
(C)
(CH)
(CH2)
(CH)
(CH3)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
(CH3)
(CH3)
(CH3)
(CH3)
(C)c
(C)c
(C)c
(C)c
(CH3)d
(C)c
(CH3)d
(C)c
(CH3)d
(CH3)
3-Ac
(CH3)d
(CH3)d
3-COPr
1′
2′
3′
4′
171.6
35.8
18.0
13.6
(C)
(CH2)
(CH2)
(CH3)
4-Ac
169.0
20.5
(C)c
(CH3)
4-COPr
1′′
2′′
3′′
4′′
171.6
36.0
18.4
13.7
169.3
20.8
170.2
21.0
(C)
171.8
35.9
18.4
13.6
169.2
20.7
170.2
20.9
(C)
171.4
35.9
18.5
13.6
169.3
20.9
170.2
20.9
(C)
(CH2)
(CH2)
(CH3)
(C)c
(CH2)
(CH2)
(CH3)
(C)c
(CH2)
(CH2)
(CH3)
(C)c
9-Ac
169.2
20.8
170.2
21.0
(C)c
(CH3)d
(C)c
(CH3)d
(C)c
(CH3)d
(C)c
(CH3)
14-Ac
(C)c
(CH3)d
(CH3)d
(CH3)d
(CH3)
a 125 MHz in CDCl3. b 100 MHz in CDCl3. c,d Data are interchangeable in the same column.
The absolute configuration of briaranolides A-D (1-4)
was determined by the use of X-ray analysis together with
chemical conversions. As mentioned above, the chemical
conversion of briaranolide D (4) yielded briaranolides B (2)
and C (3). Hydrolysis of the ester groups in briaranolide D
(4) followed by acetylation yielded briaranolide A (1). The
absolute configuration of the p-bromobenzoate 11 (Figure
2) derived from briaranolide D (4) was determined to be

1330 Journal of Natural Products, 2005, Vol. 68, No. 9
Hoshino et al.
Figure 1. Selective 1H-1H COSY and HMBC correlations of 1.
Figure 4. Selective 1H-1H COSY and HMBC correlations of 5.
(8) possesses propyonyloxy and butyryloxy groups at the
C-2 and C-3 positions, respectively, in lieu of the acetoxy
group(s) of 5.
The absolute configuration of briaranolides E-H (5-8)
was determined by the use of X-ray analysis together with
chemical conversions. Briaranolide E (5) was derived from
briaranolides F (6) and H (8) by hydrolysis followed by
acetylation and also from the acetylation of briaranolide
G (7). X-ray analysis of bis-p-bromobenzoate 12 (Figure 5),
which was derived from briaranolide D (6), confirmed the
absolute configuration as 1S,2R,3S,7S,8S,9S,10S,14S,17R
on the basis of the Flack parameter [0.00(2)] (Figure 6).14,16
Consequently, the absolute configuration of briaranolides
E-H (5-8) was clearly shown to be 1R,2R,3S,7S,8S,9S,-
10S,14S,17R.
Figure 2. Structure of p-bromobenzoate 11.
Briaranolide I (9) was found to have the molecular
formula C26H32O9 on the basis of elemental analysis. The
presence of a γ-lactone moiety (1786 cm-1) and ester group
(1748, 1731, and 1250 cm-1) was suggested from the IR
1
spectrum. From H and 13C NMR analyses, compound 9
was found to have three acetoxy groups and one γ-lactone
moiety [δH 2.12 (3H, s), 2.05 (3H, s), 2.01 (3H, s), δC 170.7
(C), 170.4 (C), 169.8 (C), 169.8 (C)], in addition to one
disubstituted E-olefin [δH 6.60 (1H, d, J ) 15.7 Hz), 5.94
(1H, dd, J ) 15.7, 9.9 Hz), δC 137.7 (CH), 126.2 (CH)] and
two trisubstituted olefins [δH 5.52 (1H, br s), 5.31 (1H, m),
δC 142.4 (C), 131.4 (C), 123.2 (CH), 117.4 (CH)] (Tables 5
and 6). The planar structure of 9 was determined by 2D
1
NMR (HMQC, H-1H COSY, and HMBC), the molecular
formula, and the C-8 (δC 68.6) and C-17 (δC 64.1) 13C NMR
chemical shifts (Figure 7).
The molecular formula of briaranolide J (10) was deter-
mined as C26H32O10 based on high-resolution ESIMS. The
presence of an 11,12-epoxide in 10 was clearly indicated
following spectroscopic comparison with 9.
The absolute configuration of briaranolide I (9) was
determined as 1R,2S,7S,8S,9S,10S,14S,17R from the chemi-
cal conversion of briaranolide G (7) using the following
three steps: (1) mesylation of 7, (2) â-elimination of the
mesylate by treatment with DBU, and (3) acetylation. The
absolute configuration of briaranolide J (10) was estab-
lished as 1R,2S,7S,8S,9S,10S,11S,12R,14S,17R as deter-
mined from its synthesis from briaranolide I (9) by epoxi-
dation and the NOESY correlation between Me-15 and
Me-20 of 10.
Figure 3. ORTEP drawing of p-bromobenzoate 11.
1R,2R,3S,4R,7S,8S,9S,10S,14S,17R on the basis of the
Flack parameter [-0.002 (6)] in the X-ray analysis (Figure
3).14,15 These results clearly indicated that each of the
briaranolides A-D (1-4) possess the same 1R,2R,3S,4R,-
7S,8S,9S,10S,14S,17R configuration.
Briaranolide E (5) was shown to have the molec-
ular formula C28H36O11 as determined by high-resolution
ESIMS. The spectral data of 5 were similar to that of
briaranolide A (1) except that one methylene was detected
in the NMR spectrum in lieu of the acyloxylated methine
of 1. The planar structure of 5 was determined by 2D
Just like briaranolides I (9) and J (10), 8,17-epoxybri-
arane diterpenoids that possess a 3,5-diene moiety are
quite rare.17 The biological activity of the 10 new briarane
diterpenoides reported here is currently under investiga-
tion.
1
NMR (HMQC, H-1H COSY, and HMBC), the molecular
formula, and the C-8 (δC 71.6) and C-17 (δC 62.2) 13C NMR
chemical shifts (Figure 4).
The molecular formulas of briaranolides F-H (6-8) were
determined as C30H40O11, C26H34O10, and C31H42O11, re-
spectively, from high-resolution ESIMS. The IR and NMR
spectra of 6-8 were similar to those of 5 (Tables 3 and 4).
The functional groups at C-2 and/or C-3 of compounds 6-8
differed from that of 5, as determined from 1D and 2D
NMR analyses. Briaranolide F (6) possesses a butyryloxy
group at the C-3 position, briaranolide G (7) possesses a
hydroxy group at the C-3 position, while briaranolide H
Experimental Section
General Experimental Procedures. Optical rotations
were measured with a JASCO DIP-360 polarimeter. IR spectra
were recorded with a JASCO FT-IR/620 spectrometer and UV
1
spectra with a JASCO V-550 spectrometer. H and 13C NMR
spectra were taken with Bruker DPX-400 and DRX-500
spectrometers. Chemical shifts were expressed on a δ (ppm)

Epoxybriarane Diterpenoids from Briareum
Journal of Natural Products, 2005, Vol. 68, No. 9 1331
Table 3. 1H NMR Data for Compounds 5-8a (J in Hz)
no.
5
6
7
8
2
3
4
5.51
4.75
3.27
2.07
5.38
5.60
5.53
3.08
5.48
2.34
2.19
4.80
1.60
1.82
1.47
1.75
2.11
(d, 3.4)
(m)
5.51
4.77
3.28
2.06
5.38
5.60
5.53
3.09
5.49
2.34
2.18
4.77
1.60
1.81
1.47
1.76
2.10
(d, 3.4)
(m)
5.45
3.51
3.25
1.92
5.33
5.58
5.48
3.05
5.41
2.36
2.21
4.80
1.60
1.93
1.46
1.68
2.14
(d, 3.6)
(br s)
5.55
4.78
3.29
2.07
5.39
5.61
5.54
3.09
5.50
2.36
2.19
4.78
1.60
1.81
1.47
1.76
(d, 3.3)
(m)
(dd, 15.5, 3.7)
(dd, 15.5, 2.9)
(br d, 9.1)
(d, 9.1)
(br s)
(br s)
(br s)
(m)
(m)
(dd, 15.6, 3.9)
(dd, 15.6, 3.0)
(br d, 8.9)
(d, 9.2)
(d, 1.6)
(br s)
(br s)
(m)
(m)
(dd, 9.3, 6.9)
(s)
(d, 0.6)
(s)
(d, 0.7)
(s)
(dd, 15.5, 3.8)
(dd,15.5, 2.9)
(br d, 9.2)
(d, 9.2)
(d, 1.5)
(br s)
(dd, 15.0, 3.2)
(dd, 15.0, 2.6)
(br d, 9.1)
(d, 9.1)
(d, 1.4)
(br s)
(br s)
(m)
(m)
6
7
9
10
12
13
(br s)
(m)
(m)
14
(m)
(dd, 9.3, 6.9)
(s)
(dd, 9.5, 6.9)
(s)
15
(s)
16
(br s)
(br s)
(br s)
18
(s)
(s)
(s)
20
(br s)
(br s)
(br s)
2-Ac
2-COEt
(s)b
(s)
2′
3′
2.36
1.19
(m)
(t, 7.6)
3-Ac
3-COPr
1.97
(s)
2′′
3′′
4′′
0.92
1.61
2.20
2.18
1.97
(t, 7.4)
(m)
2.18
1.61
0.92
2.18
1.95
(t, 7.4)
(m)
(t, 7.4)
(s)
(s)
(t, 7.4)
9-Ac
14-Ac
2.18
1.98
(s)
(s)
(s)b
2.18
2.00
(s)
(s)
(s)
a 500 MHz in CDCl3. b Data are interchangeable in the same column.
Table 4. 13C NMR Data for Compounds 5-8a
no.
5
6
7
8
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2-Ac
41.9 (C)
72.3 (CH)
72.5 (CH)
42.0 (C)
72.3 (CH)
72.2 (CH)
42.0 (C)
75.1 (CH)
72.6 (CH)
36.5 (CH2) 33.9 (CH2)
143.6 (C) 142.5 (C)
42.0 (C)
72.4 (CH)
72.1 (CH)
33.7 (CH2) 33.9 (CH2)
142.5 (C) 142.5 (C)
121.5 (CH) 121.5 (CH) 120.6 (CH) 121.5 (CH)
75.9 (CH)
71.6 (C)
72.6 (CH)
44.0 (CH)
130.9 (C)
122.1 (CH) 122.1 (CH) 121.9 (CH) 122.2 (CH)
28.1 (CH2) 28.1 (CH2) 28.2 (CH2) 28.1 (CH2)
73.4 (CH) 73.4 (CH) 73.4 (CH) 73.4 (CH)
17.0 (CH3) 17.0 (CH3)
23.4 (CH3) 23.4 (CH3)
76.0 (CH)
71.6 (C)
72.7 (CH)
44.0 (CH)
130.9 (C)
76.1 (CH)
71.6 (C)
72.7 (CH)
43.6 (CH)
131.5 (C)
76.0 (CH)
71.6 (C)
72.6 (CH)
44.0 (CH)
130.9 (C)
Figure 5. Structure of bis-p-bromobenzoate 12.
16.9 (CH3) 17.0 (CH3)
23.3 (CH3) 23.4 (CH3)
62.2 (C)
10.5 (CH3) 10.5 (CH3)
171.3 (C) 171.3 (C)
21.9 (CH3) 21.7 (CH3)
170.9 (C)
62.2 (C)
10.5 (CH3) 10.5 (CH3)
171.3 (C) 171.3 (C)
21.7 (CH3) 21.7 (CH3)
62.2 (C)
62.2 (C)
169.3 (C)
169.2 (C)b
20.9 (CH3) 20.9 (CH3)b 21.1 (CH3)
2-COEt 1′
172.5 (C)
27.7 (CH2)
9.2 (CH3)
2′
3′
3-Ac
169.6 (CH3)
20.7 (C)
3-COPr 1′′
172.2 (C)
35.9 (CH2)
18.0 (CH2)
13.6 (CH3)
172.1 (C)
35.9 (CH2)
17.9 (CH2)
13.6 (CH3)
169.2 (C)
2′′
3′′
4′′
Figure 6. ORTEP drawing of bis-p-bromobenzoate 12.
9-Ac
169.2 (C)
169.2 (C)b
169.3 (C)
on Bruker MXC18 KHF22 and Rigaku RAXIS-RAPID diffrac-
tometers. Flash column chromatography was carried out on
Kanto Chemical silica gel 60N (spherical, neutral) 40-50 µm.
Animal Material. The gorgonian specimens of Briareum
sp. were obtained from the coral reef of Hatoma Island,
Okinawa, Japan, at a depth of 5 m by hand using scuba, in
June 2002. A voucher specimen has been deposited at Tokyo
University of Pharmacy and Life Science (SC-02-10).
Extraction and Isolation. Wet specimens (10.3 kg) were
cut into small pieces and extracted with MeOH (15.0 L × 3)
and then acetone (15.0 L × 3). The combined extract (574 g)
was concentrated and partitioned between EtOAc (4.0 L × 4)
and water (2.0 L) to give an EtOAc-soluble portion (265 g).
The EtOAc-soluble portion was partitioned between n-hexane
(1.8 L × 4) and 80% aqueous MeOH (3.0 L) to give a n-hexane-
20.7 (CH3) 20.7 (CH3)b 20.7 (CH3) 20.7 (CH3)
14-Ac
170.2 (C)
20.9 (CH3) 20.9 (CH3)
170.2 (C)
170.2 (C)
21.0 (CH3) 20.9 (CH3)
170.2 (C)
a 125 MHz in CDCl3. b Data are interchangeable in the same
column.
scale with tetramethylsilane (TMS) as the internal standard
(s, singlet; d, doublet; t, triplet; m, multiplet; br, broad). EIMS
spectra were obtained with a Thermo Quest TSQ 700 spec-
trometer and high-resolution EIMS (HREIMS) spectra, using
a VG Auto Spec E spectrometer. ESIMS and high-resolution
ESIMS (HRESIMS) spectra were obtained with a Micromass
LCT spectrometer. Elemental analysis data were obtained
with an Elemental Vavio EL. X-ray diffractions were measured

1332 Journal of Natural Products, 2005, Vol. 68, No. 9
Table 5. 1H NMR Data for Compounds 9 and 10 (J in Hz)
Hoshino et al.
g) and F (6) (44.3 g). Flash Si gel column chromatography of
fraction 2-4 (elution with CHCl3-EtOAc (8:1)) produced bri-
aranolide E (5) (36.9 g). Fraction 3 was subjected to flash Si
gel column chromatography (elution with CHCl3-EtOAc (3:
1)) to give fractions 3-1 (1.39 g), 3-2 (16.8 g), 3-3 (8.96 g), 3-4
(13.9 g), and 3-5 (4.34 g). Flash Si gel column chromatography
of fraction 3-2 (elution with n-hexane-EtOAc (1:1)) afforded
briaranolides A (1) (2.64 g) and D (4) (7.78 g). Fraction 3-3
was chromatographed repeatedly on flash Si gel using n-hex-
ane-EtOAc (1:1) and n-hexane-acetone (2:1) to give briara-
nolides G (7) (346 mg) and J (10) (293 mg).
no.
9a
10b
2
3
4
6
7
9
10
12
13
5.50
5.94
6.60
5.31
4.66
6.50
2.81
5.52
2.30
2.00
4.87
1.12
1.85
1.61
1.89
2.01
2.12
2.05
(d, 9.9)
(dd, 15.7, 9.9)
(d, 15.7)
(m)
(d, 4.4)
(br s)
(br s)
(br s)
(m)
(m)
(br d, 4.4)
(s)
(br s)
(s)
5.45
5.85
6.60
5.33
4.71
6.36
2.59
2.93
2.18
(d, 10.1)
(dd, 15.7, 10.1)
(d, 15.7)
(m)
(d, 4.7)
(s)
(s)
(br s)
(m)
Briaranolide A (1): colorless powder; mp 230-233 °C;
[R]D +41.2° (c 1.0, CHCl3); IR (KBr) νmax 1793, 1744, 1238
27
14
4.79
1.19
1.87
1.67
1.35
2.00
2.17
2.05
(br d, 2.5)
(s)
cm-1; 1H and13C NMR, see Tables 1 and 2; COSY correlations
(H/H) H-2/H-3; H-3/H-4; H-6/H-7, H-9/H-10; H-12/H-13 (δH
2.32), H-13 (δH 2.16); H-13 (δH 2.32)/H-14; H-13 (δH 2.16)/
H-14; HMBC correlations (H/C) H-2/C-1, C-3, C-4, C-10, C-14,
Me-15; H-4/C-3, C-5, C-6, Me-16, C-4-Ac; H-6/C-4, Me-16; H-7/
C-5, C-6, C-19; H-9/C-1, C-7, C-8, C-10, C-11; H-10/C-1, C-2,
C-8, C-9, C-11, C-12, C-14, Me-20; H-12/C-10, C-13, Me-20;
H-13 (δH 2.32)/C-1, C-11, C-12; H-13 (δH 2.16)/C-11, C-12, C-14;
H-14/C-1, C-10, C-12, C-13, Me-15, C-14-Ac; Me-16/C-4, C-5,
C-6; Me-18/C-8, C-17, C-19; Me-20/C-10, C-11, C-12; C-4-Ac-
(Me)/C-4-Ac(CdO); C-14-Ac(Me)/C-14-Ac(CdO); ESIMS (m/z)
607 [M+ + H] (30), 547 (100); HRESIMS (m/z) 607.2405 (calcd
for C30H39O13, M+ + H, 607.2391).
15
16
(br s)
(s)
18
20
(br s)
(s)
(s)
(s)
(s)
2-Ac
9-Ac
14-Ac
(s)
(s)
(s)
a 400 MHz in CDCl3. b 500 MHz in CDCl3.
Table 6. 13C NMR Data for Compounds 9 and 10
no.
9a
10b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2-Ac
45.0
73.9
(C)
44.9
74.2
126.0
137.6
142.5
116.8
76.6
67.8
68.4
40.4
58.4
59.2
26.1
70.8
14.5
23.4
63.4
9.1
170.7
24.3
169.6
21.2
170.0
21.1
170.5
21.1
(C)
(CH)
(CH)
(CH)
(C)
(CH)
(CH)
(CH)
(C)
Briaranolide B (2): colorless needles; mp 224-228 °C;
[R]D +50.4° (c 0.4, CHCl3); IR (KBr) νmax 1793, 1743, 1240
24
126.2
137.7
142.4
117.4
77.0
cm-1; 1H and13C NMR, see Tables 1 and 2; COSY correlations
(H/H) H-2/H-3; H-3/H-4; H-6/H-7, H-9/H-10; H-12/H-13 (δH
2.32), H-13 (δH 2.14); H-13 (δH 2.32)/H-14; H-13 (δH 2.14)/
H-14; H-2′′/H-3′′; H-3′′/Me-4′′; HMBC correlations (H/C) H-2/
C-1, C-3, C-4, C-14, Me-15; H-4/C-3, C-5, C-6, Me-16, C-4-
COPr; H-6/C-4, Me-16; H-7/C-5, C-6, C-19; H-9/C-1, C-7, C-8,
C-10, C-11; H-10/C-1, C-8, C-11, C-12, C-14, Me-20; H-12/
C-10, C-13, C-14, Me-20; H-13 (δH 2.26)/C-1, C-11, C-12; H-13
(δH 2.14)/C-11, C-12, C-14; H-14/C-1, C-2, C-10, C-13, Me-15,
C-14-Ac; Me-16/C-4, C-5, C-6; Me-18/C-8, C-17, C-19; Me-20/
C-10, C-11, C-12; H-2′′/C-1′′, C-3′′, Me-4′′; H-3′′/C-1′′, C-2′′,
Me-4′′; Me-4′′/C-2′′, C-3′′; C-14-Ac(Me)/C-14-Ac(CdO); ESIMS
(m/z) 657 [M+ + Na] (60), 652 (100), 635 (25), 575 (38),
385 (68), 325 (80); HRESIMS (m/z) 657.2535 (calcd for
C32H42O13Na, M+ + Na, 657.2523).
(CH)
(CH)
(C)
(CH)
(CH)
(C)
(CH)
(CH2)
(CH)
(CH3)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
(CH)
(CH)
(C)
(CH)
(CH)
(C)
(CH)
(CH2)
(CH)
(CH3)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
(CH3)
(C)
68.6
68.1
39.3
131.4
123.2
28.1
71.3
13.8
23.3
64.1
10.8
170.7
24.5
Briaranolide C (3): colorless pillars; mp 149-152 °C; [R]
169.8
21.2
169.8
21.0
170.4
21.1
D
25 +44.3° (c 1.1, CHCl3); IR (KBr) νmax 1795, 1745, 1244 cm-1
;
1H and13C NMR, see Tables 1 and 2; COSY correlations (H/H)
H-2/H-3; H-3/H-4; H-6/H-7, H-9/H-10; H-12/H-13 (δH 2.28),
H-13 (δH 2.13); H-13 (δH 2.28)/H-14; H-13 (δH 2.13)/H-14; H-2′/
H-3′; H-3′/Me-4′; H-2′′/H-3′′; H-3′′/Me-4′′; HMBC correlations
(H/C) H-2/C-1, C-3, C-4, C-14, Me-15; H-4/C-3, C-5, C-6,
Me-16, C-4-COPr; H-6/C-4, C-5, Me-16; H-7/C-5, C-6, C-19;
H-9/C-1, C-7, C-8, C-10, C-11; H-10/C-1, C-8, C-11, C-12, C-14,
Me-20; H-12/C-10, C-13; H-13 (δH 2.28)/C-11; H-13 (δH 2.13)/
C-11, C-14; H-14/C-1, C-13, C-14-Ac; Me-15/C-1, C-10; Me-16/
C-4, C-5, C-6; Me-18/C-8, C-17, C-19; Me-20/C-10, C-11, C-12;
H-2′/C-1′, C-3′; H-3′/C-1′, C-2′, Me-4′; Me-4′/C-2′, C-3′; H-2′′/
C-1′′, C-3′′; H-3′′/C-1′′, C-2′′, Me-4′′; Me-4′′/C-2′′, C-3′′; C-14-
Ac(Me)/C-14-Ac(CdO); EIMS (m/z) 663 [M+ + H] (10), 603 (45),
575 (72), 515 (100); anal. C 61.55%, H 7.04%, calcd for
C34H46O13, C 61.62%, H 7.00%.
9-Ac
(CH3)
(C)
(CH3)
(CH3)
(C)
(CH3)
14-Ac
a 100 MHz in CDCl3. b 125 MHz in CDCl3.
Figure 7. Selective 1H-1H COSY and HMBC correlations of 9.
23
Briaranolide D (4): colorless amorphous solid; [R]D
+53.0° (c 1.0, CHCl3); IR (KBr) νmax 3452, 1790, 1740, 1245
cm-1; 1H and13C NMR, see Tables 1 and 2; COSY correlations
(H/H) H-6/H-7, H-9/H-10; H-12/H-13; H-13/H-14; H-2′′/H-3′′;
H-3′′/Me-4′′; HMBC correlations (H/C) H-4/C-3, C-5, C-6,
Me-16, C-4-COPr; H-6/C-5, C-7, Me-16; H-7/C-5, C-6, C-19;
H-9/C-1, C-7, C-8, C-10, C-11, C-9-Ac; H-10/C-1, C-2, C-8, C-11,
C-12; H-12/C-13, Me-20; H-13/C-11, C-12, C-14; H-14/C-1, C-10,
C-12, C-13, Me-15, C-14-Ac; Me-16/C-4, C-5, C-6; Me-18/
C-8, C-17, C-19; Me-20/C-10, C-11, C-12; H-2′′/C-1′′, C-3′′,
Me-4′′; H-3′′/C-1′′, C-2′′, Me-4′′; Me-4′′/C-2′′, C-3′′; C-2-Ac(Me)/
C-2-Ac(CdO); C-9-Ac(Me)/C-9-Ac(CdO); C-14-Ac(Me)/C-14-Ac-
(CdO); ESIMS (m/z) 593 [M++H] (10), 575 (100), 533 (20);
HRESIMS (m/z) 593.2614 (calcd for C30H41O12, M+ + H,
593.2598).
soluble portion (88.0 g) and an 80% aqueous MeOH-soluble
portion (171 g). The 80% aqueous MeOH-soluble portion was
chromatographed on Si gel using a n-hexane-EtOAc (1:1, 1:3,
to 0:1) gradient and MeOH as eluent to produce fractions 1
(2.60 g), 2 (113 g), 3 (45.7 g), and 4 (8.10 g). Fraction 2 was
subjected to flash Si gel column chromatography (elution with
n-hexane-EtOAc (5:4)) to give fractions 2-1 (1.10 g), 2-2 (9.20
g), 2-3 (65.4 g), and 2-4 (37.3 g). Fraction 2-2 was subjected to
flash Si gel column chromatography (elution with n-hexane-
EtOAc (5:4)) and then recrystallized from Et2O-n-hexane to
give briaranolides C (3) (3.36 g), H (8) (501 mg), and I (9) (1.03
g). Flash Si gel column chromatography of fraction 2-3 (elution
with CHCl3-EtOAc (10:1)) afforded briaranolides B (2) (13.1

Epoxybriarane Diterpenoids from Briareum
Journal of Natural Products, 2005, Vol. 68, No. 9 1333
Briaranolide E (5): colorless needles; mp 183-187 °C;
cm-1; 1H and13C NMR, see Tables 5 and 6; COSY correlations
(H/H) H-2/H-3; H-3/H-4; H-6/H-7, H-9/H-10; H-12/H-13 (δH
2.30), H-13 (δH 2.00); H-13 (δH 2.30)/H-14; H-13 (δH 2.00)/
H-14; HMBC correlations (H/C) H-2/C-1, C-3, C-4, C-14,
Me-15, C-2-Ac; H-3/C-1, C-2, C-5; H-4/C-2, C-3, C-5, C-6; H-6/
C-4, C-7, C-8; H-7/C-5, C-6, C-8, C-19; H-9/C-1, C-8, C-10, C-11,
C-17, C-9-Ac; H-10/C-1, C-9, C-11, C-12; H-13 (δH 2.30)/C-11,
C-12; H-13 (δH 2.00)/C-1, C-11; H-14/C-1, C-2, C-10, C-12, C-13,
C-14-Ac; Me-15/C-1, C-2, C-10, C-14; Me-16/C-4, C-5, C-6;
Me-18/C-8, C-17, C-19; Me-20/C-10, C-11, C-12; C-2-Ac(Me)/
C-2-Ac(CdO); C-9-Ac(Me)/C-9-Ac(CdO); C-14-Ac(Me)/C-14-Ac-
(CdO); EIMS (m/z) 488 [M+] (18), 446 (62), 386 (7), 326 (17);
anal. C 63.81%, H 6.73%, calcd for C26H32O9, C 63.92%, H
6.60%.
26
[R]D -26.0° (c 1.0, CH2Cl2); IR (KBr) νmax 1790, 1745, 1242
cm-1; 1H and13C NMR, see Tables 3 and 4; COSY correlations
(H/H) H-2/H-3, H-3/H-4 (δH 3.27), H-4 (δH 2.07); H-6/H-7, H-9/
H-10; H-12/H-13 (δH 2.34), H-13 (δH 2.19); H-13 (δH 2.34)/
H-14; H-13 (δH 2.19)/H-14; HMBC correlations (H/C) H-2/C-1,
C-4, C-14, Me-15, C-2-Ac; H-4 (δH 3.27)/C-3, C-5, C-6, Me-16;
H-4 (δH 2.07)/C-3, C-5, C-6; H-6/C-4, Me-16; H-7/C-5, C-6, C-19;
H-9/C-1, C-7, C-8, C-10, C-11, C-9-Ac; H-10/C-1, C-8, C-11,
C-12, C-14, Me-20; H-13 (δH 2.34)/C-1, C-11, C-12; H-13 (δH
2.19)/C-14; H-14/C-1, C-2, C-13, Me-15, C-14-Ac; Me-15/C-1,
C-2, C-10, C-14; Me-16/C-4, C-5, C-6; Me-18/C-8, C-17, C-19;
Me-20/C-10, C-11, C-12; C-2-Ac(Me)/C-2-Ac(CdO); C-3-Ac(Me)/
C-3-Ac(CdO); C-9-Ac(Me)/C-9-Ac(CdO); C-14-Ac(Me)/C-14-Ac-
(CdO); ESIMS (m/z) 571 [M+ + Na] (100), 369 (25), 309 (58);
HRESIMS (m/z) 571.2125 (calcd for C28H36O11Na, M+ + Na,
571.2155).
Briaranolide J (10): colorless amorphous; [R]D24 +11.8° (c
1
1.0, CHCl3); IR (KBr) νmax 1795, 1742, 1233 cm-1; H and13C
NMR, see Tables 5 and 6; COSY correlations (H/H) H-2/H-3,
H-3/H-4; H-6/H-7, H-9/H-10; H-12/H-13; H-13/H-14; HMBC
correlations (H/C) H-2/C-1, C-3, C-4, C-14, Me-15, C-2-Ac; H-3/
C-1, C-2, C-5; H-4/C-2, C-3, C-5, C-6, Me-16; H-6/C-4, C-7, C-8,
Me-16; H-7/C-5, C-6, C-19; H-9/C-1, C-8, C-10, C-11, C-17, C-9-
Ac; H-10/C-1, C-8, C-9, C-11, C-14, Me-15, Me-20; H-12/C-13,
C-14, Me-20; H-13/C-1, C-12, C-14; H-14/C-2, C-10, C-12, C-13,
C-14-Ac; Me-15/C-1, C-2, C-10, C-14; Me-16/C-4, C-5, C-6;
Me-18/C-8, C-17, C-19; Me-20/C-10, C-11, C-12; C-2-Ac(Me)/
C-2-Ac(CdO); C-9-Ac(Me)/C-9-Ac(CdO); C-14-Ac(Me)/C-14-Ac-
(CdO); NOESY correlations (H/H) H-2/H-4, H-10, C-14-Ac;
H-3/Me-15, Me-16, C-9-Ac; H-4/Me-16; H-6/H-7, Me-16; H-7/
H-9, C-9-Ac; H-9/H-10, Me-18, Me-20; H-10/Me-18; H-12/
Me-15, Me-20; H-14/Me-15, C-2-Ac; Me-15/Me-20; Me-18/
Me-20; ESIMS (m/z) 505 [M+ + H] (65), 445 (100), 320 (60),
268 (32); HRESIMS (m/z) 505.2063 (calcd for C26H33O10, M+
+ H, 505.2074).
Briaranolide F (6): colorless needles; mp 130-135 °C;
28
[R]D -50.3° (c 1.0, CHCl3); IR (KBr) νmax 1789, 1743, 1249
cm-1; 1H and13C NMR, see Tables 3 and 4; COSY correlations
(H/H) H-2/H-3; H-3/H-4 (δH 3.28), H-4 (δH 2.06); H-6/H-7, H-9/
H-10; H-12/H-13 (δH 2.34), H-13 (δH 2.18); H-13 (δH 2.34)/
H-14; H-13 (δH 2.18)/H-14; H-2′′/H-3′′; H-3′′/Me-4′′; HMBC
correlations (H/C) H-2/C-1, C-4, Me-15; H-3/C-5, C-3-COPr; H-4
(δH 3.28)/C-2, C-3, C-5, C-6, Me-16; H-4 (δH 2.06)/C-2, C-3, C-5,
C-6, Me-16; H-6/C-4, Me-16; H-7/C-5, C-6, C-19; H-9/C-1, C-7,
C-8, C-10, C-11; H-10/C-1, C-2, C-8, C-11, C-12, Me-20; H-12/
C-10, C-14, Me-20; H-13 (δH 2.34)/C-11, C-12; H-13 (δH 2.18)/
C-11, C-12, C-14; H-14/C-1, C-2, C-13, Me-15, C-14-Ac;
Me-15/C-1, C-10, C-14; Me-16/C-4, C-5, C-6; Me-18/C-8, C-17,
C-19; Me-20/C-10, C-11, C-12; H-2′′/C-1′′, C-3′′, Me-4′′; H-3′′/
C-1′′, C-2′′, Me-4′′; Me-4′′/C-2′′, C-3′′; C-14-Ac(Me)/C-14-Ac-
(CdO); ESIMS (m/z) 577 [M+ + H] (80), 517 (100), 457 (68),
369 (70), 309 (69); HRESIMS (m/z) 577.2637 (calcd for C30H41O11,
M+ + H, 577.2649).
Synthesis of Briaranolide B (2) from Briaranolide D
(4). To a pyridine (200 µL) solution of 4 (10.1 mg, 17.0 µmol)
was added acetic anhydride (100 µL), and the mixture was
stirred at room temperature for 14 h. The reaction mixture
was concentrated under reduced pressure and then purified
by Si gel column chromatography (elution with n-hexane-
EtOAc (2:1)) to give 2 (7.5 mg, 70% yield). The spectral data
were identical with those of natural 2.
Synthesis of Briaranolide B (3) from Briaranolide D
(4). To a pyridine (170 µL) solution of 4 (19.8 mg, 33.4 µmol)
was added n-butyryl chloride (8.7 µL, 83.5 µmol), and the
mixture was stirred at room temperature. After 11 h, 4-(dim-
ethylamino)pyridine (0.5 mg) was added, and stirring was
continued for 5 h at room temperature. The reaction mixture
was diluted with diethyl ether and washed with water and
brine. The organic layer was dried over anhydrous magnesium
sulfate and concentrated under reduced pressure. The residue
was purified by Si gel column chromatography (elution with
n-hexane-EtOAc (2:1)) to give 3 (14.6 mg, 66% yield). The
spectral data were identical with those of natural 3.
Synthesis of Briaranolide A (1) from Briaranolide D
(4). To a methanol (1.0 mL) solution of 4 (30.0 mg, 50.6 µmol)
was added lithium hydroxide monohydrate (2.0 mg, 50.6 µmol),
and the mixture was stirred at room temperature for 1 h. The
reaction mixture was concentrated under reduced pressure.
To a solution of the residue in pyridine (400 µL) were added
acetic anhydride (200 µL) and 4-(dimethylamino)pyridine (3.1
mg, 25.3 µmol) followed by stirring at 60 °C for 20 h. The
mixture was concentrated under reduced pressure and then
purified by Si gel column chromatography (elution with
n-hexane-EtOAc (1:1)) to give 1 (20.1 mg, 67% yield). The
spectral data were identical with those of natural 1.
Synthesis of p-Bromobenzoate 11 from Briaranolide
D (4). To a pyridine (400 µL) solution of 4 (50.0 mg, 84.4 µmol)
was added p-bromobenzoyl chloride (37.1 mg, 169 µmol), and
the mixture was stirred at room temperature for 20 h. The
reaction mixture was diluted with diethyl ether and washed
with water, aqueous HCl (1 M), and brine. The organic layer
was dried over anhydrous magnesium sulfate and concentrated
under reduced pressure. The residue was purified by Si gel
column chromatography (elution with n-hexane-EtOAc (2:1))
to give p-bromobenzoate 11 (49.9 mg, 76% yield): colorless
Briaranolide G (7): colorless amorphous solid; [R]D25 +3.0°
1
(c 1.0, CHCl3); IR (KBr) νmax 3465, 1788, 1742, 1246 cm-1; H
and13C NMR, see Tables 3 and 4; COSY correlations (H/H)
H-2/H-3, H-3/H-4 (δH 3.25), H-4 (δH 1.92); H-6/H-7, H-9/H-10;
H-12/H-13 (δH 2.36), H-13 (δH 2.21); H-13 (δH 2.36)/H-14; H-13
(δH 2.21)/H-14; HMBC correlations (H/C) H-2/C-4, C-10, C-14,
Me-15, C-2-Ac; H-3/C-5; H-4 (δH 3.25)/C-2, C-5, C-6, Me-16;
H-4 (δH 1.92)/C-2, C-6, Me-16; H-6/C-4, C-8, Me-16; H-7/C-5,
C-6, C-19; H-9/C-1, C-7, C-8, C-10, C-11, C-9-Ac; H-10/C-1, C-2,
C-8, C-9, C-11, C-12, C-14, Me-20; H-12/C-10, C-13, C-14,
Me-20; H-13 (δH 2.36)/C-1, C-11, C-12, C-14; H-13 (δH 2.21)/
C-11, C-12, C-14; H-14/C-1, C-2, C-13, Me-15, C-14-Ac;
Me-15/C-1, C-2, C-10, C-14; Me-16/ C-4, C-5, C-6; Me-18/C-8,
C-17, C-19; Me-20/C-10, C-11, C-12; C-2-Ac(Me)/C-2-Ac(CdO);
C-9-Ac(Me)/C-9-Ac(CdO); C-14-Ac(Me)/C-14-Ac(CdO); ESIMS
(m/z) 507 [M+ + H] (100), 489 (32), 447 (87), 387 (30);
HRESIMS (m/z) 507.2242 (calcd for C26H35O10, M+ + H,
507.2230).
Briaranolide H (8): colorless needles; mp 207-210 °C;
26
[R]D -39.8° (c 1.0, CHCl3); IR (KBr) νmax 1789, 1752, 1735,
1246 cm-1 1H and13C NMR, see Tables 3 and 4; COSY
;
correlations (H/H) H-2/H-3; H-3/H-4 (δH 3.29), H-4 (δH 2.07);
H-6/H-7, H-9/H-10; H-12/H-13 (δH 2.36), H-13 (δH 2.19); H-13
(δH 2.36)/H-14; H-13 (δH 2.19)/H-14; H-2′/H-3′; H-2′′/Me-3′′;
H-3′′/Me-4′′; HMBC correlations (H/C) H-2/C-1, C-4, C-14,
Me-15, C-2-COEt; H-3/C-5, C-3-COPr; H-4 (δH 3.29)/C-2, C-5,
C-6, Me-16; H-4 (δH 2.07)/C-2, C-5, C-6, Me-16; H-6/C-4,
Me-16; H-7/C-5, C-6, C-19; H-9/C-7, C-8, C-10, C-11, C-9-Ac;
H-10/C-1, C-8, C-11, C-12, C-14, Me-20; H-12/C-10, C-14,
Me-20; H-13 (δH 2.36)/C-1, C-11, C-12; H-13 (δH 2.19)/C-11,
C-12, C-14; H-14/C-1, C-2, C-13, Me-15, C-14-Ac; Me-15/C-1,
C-2, C-10, C-14; Me-16/C-4, C-5, C-6; Me-18/C-8, C-17, C-19;
Me-20/C-10, C-11, C-12; H-2′/C-1′, Me-3′; Me-3′/C-1′, C-2′; H-2′′/
C-1′′, C-3′′, Me-4′′; H-3′′/C-1′′, C-2′′, Me-4′′; Me-4′′/C-2′′, C-3′′;
C-9-Ac(Me)/C-9-Ac(CdO); C-14-Ac(Me)/C-14-Ac(CdO); ESIMS
(m/z) 591 [M+ + H] (80), 531 (100), 471 (55), 369 (60), 309 (70);
HRESIMS (m/z) 591.2809 (calcd for C31H43O11, M+ + H,
591.2805).
25
Briaranolide I (9): colorless prisms; mp 213-216 °C; [R]D
+33.6° (c 1.1, CHCl3); IR (KBr) νmax 1786, 1748, 1731, 1250

1334 Journal of Natural Products, 2005, Vol. 68, No. 9
Hoshino et al.
crystal; mp 103-106 °C; [R]D28 +36.0° (c 1.8, CHCl3); IR (KBr)
max
concentrated under reduced pressure. The residue was purified
by Si gel column chromatography (elution with CHCl3-acetone
(24:1)) to give bis-p-bromobenzoate 12 (12.7 mg, 47% yield):
colorless crystal; mp 198-200 °C; [R]D25 +19.1° (c 1.6, CHCl3);
IR (KBr) νmax 3583, 1784, 1755, 1716, 1590, 1272 cm-1; UV
(EtOH) λ max (ꢀ) 245 (31903) nm; 1H NMR (400 MHz, CDCl3) δ
ppm 7.94 (2H, d, J ) 8.5 Hz), 7.86 (2H, d, J ) 8.5 Hz), 7.63
(2H, d, J ) 8.5 Hz), 7.57 (2H, d, J ) 8.5 Hz), 5.68 (1H, d, J )
9.2 Hz), 5.61 (1H, d, J ) 2.1 Hz), 5.52 (1H, br s), 5.45 (1H, d,
J ) 9.2 Hz), 5.12 (1H, dd, J ) 8.2, 6.6 Hz), 5.09 (1H, br s),
4.32 (1H, br s), 3.48 (1H, dd, J ) 15.4, 4.1 Hz), 3.27 (1H, br s),
2.55 (1H, m), 2.27 (3H, s), 2.19 (2H, m), 1.86 (3H, br s), 1.82
(3H, br s), 1.62 (3H, br s), 1.51 (3H, s); 13C NMR (100 MHz,
CDCl3) δ ppm 171.3, 169.2, 165.5, 164.5, 142.2, 132.1, 132.0,
132.0, 131.9, 131.9, 131.2, 131.2, 131.1, 131.1, 129.0, 128.8,
128.5, 128.4, 121.9, 121.5, 77.2, 75.8, 75.7, 75.2, 72.4, 71.4, 62.3,
43.9, 43.2, 33.8, 28.5, 23.8, 22.2, 20.9, 17.0, 10.5; ESIMS (m/z)
787 [M+ + H] (10), 271 (100); HRESIMS (m/z) 787.0746 (calcd
for C36H37O10Br2, M+ + H, 787.0753).
ν
1794, 1740, 1591, 1375, 1271, 1243, 1224 cm-1; UV
(EtOH) λ max (ꢀ) 247 (24775) nm; 1H NMR (400 MHz, CDCl3) δ
ppm 7.81 (2H, br d, J ) 8.6 Hz), 7.60 (2H, br d, J ) 8.6 Hz),
6.56 (1H, br d, J ) 4.7 Hz), 5.88 (1H, d, J ) 9.3 Hz), 5.54 (1H,
br d, J ) 9.3 Hz), 5.50 (1H, d, J ) 2.9 Hz), 5.49 (1H, br s),
5.49 (1H, d, J ) 2.7 Hz), 5.40 (1H, br s), 4.79 (1H, t, J ) 7.7
Hz), 3.18 (1H, br s), 2.34 (1H, m), 2.20 (3H, s), 2.19 (3H, m),
2.11 (3H, br s), 2.00 (3H, s), 1.87 (3H, br s), 1.82 (3H, br s),
1.60 (3H, br s), 1.59 (2H, m), 1.49 (3H, s), 0.90 (3H, t, J ) 7.3
Hz); 13C NMR (100 MHz, CDCl3) δ ppm 171.7, 170.8, 170.2,
169.2, 169.0, 164.0, 140.3, 131.9, 131.9, 131.4, 131.1, 131.1,
128.7, 128.2, 124.7, 122.0, 77.2, 74.5, 74.3, 72.3, 71.7, 71.2, 66.0,
62.2, 43.6, 42.7, 35.9, 28.1, 22.4, 21.1, 20.9, 20.9, 18.3, 18.1,
17.7, 13.6, 10.2; ESIMS (m/z) 775 [M+ + H] (13), 716 (43), 686
(38); HRESIMS (m/z) 775.1964 (calcd for C37H44O13Br, M+
H, 775.1965).
+
Synthesis of Briaranolide E (5) from Briaranolide F
(6). To a methanol (170 µL) solution of 6 (5.0 mg, 8.7 µmol)
was added potassium carbonate (4.8 mg, 34.8 µmol), and the
mixture was stirred at room temperature for 12 h. The reaction
mixture was concentrated under reduced pressure. To a
solution of the residue in pyridine (170 µL) were added acetic
anhydride (85 µL) and 4-(dimethylamino)pyridine (2.1 mg, 17.4
µmol) followed by stirring at 40 °C for 2 days. The mixture
was concentrated under reduced pressure and then purified
by Si gel column chromatography (elution with n-hexane-
EtOAc (5:4)) to give 5 (3.0 mg, 63% yield). The spectral data
were identical with those of natural 5.
Synthesis of Briaranolide E (5) from Briaranolide G
(7). To a pyridine (200 µL) solution of 7 (5.0 mg, 9.9 µmol)
was added acetic anhydride (100 µL), and the mixture was
stirred at room temperature for 63 h. The reaction mixture
was concentrated under reduced pressure and then purified
by Si gel column chromatography (elution with n-hexane-
EtOAc (1:1)) to give 5 (5.4 mg, quant.). The spectral data were
identical with those of natural 5.
Synthesis of Briaranolide E (5) from Briaranolide H
(8). To a methanol (170 µL) solution of 8 (5.0 mg, 8.3 µmol)
was added potassium carbonate (46.0 mg, 332 µmol), and the
mixture was stirred at room temperature for 2 h. The reaction
mixture was concentrated under reduced pressure. To a
solution of the residue in pyridine (170 µL) were added acetic
anhydride (85 µL) and 4-(dimethylamino)pyridine (2.0 mg, 16.6
µmol) followed by stirring at 40 °C for 6 days. The mixture
was concentrated under reduced pressure and then purified
by Si gel column chromatography (elution with n-hexane-
EtOAc (5:4)) to give 5 (1.3 mg, 28% yield). The spectral data
were identical with those of natural 5.
Synthesis of Briaranolide I (9) from Briaranolide G
(7). To a solution of 7 (9.8 mg, 19.3 µmol) in dichloromethane
(100 µL) were added triethylamine (26.9 µL, 193 µmol) and
methanesulfonyl chloride (7.5 µL, 96.7 µmol) followed by
stirring at room temperature for 1 h. The reaction mixture
was diluted with diethyl ether, washed with water and brine,
dried over anhydrous magnesium sulfate, and concentrated
under reduced pressure. The residue was purified by Si gel
column chromatography (elution with CHCl3-acetone (19:1))
to give mesylate (11.3 mg, quant.): colorless amorphous solid;
[R]D24 -9.0° (c 0.6, CHCl3); IR (KBr) νmax 1791, 1747 cm-1; 1H
NMR (400 MHz, CDCl3) δ ppm 5.63 (1H, d, J ) 3.1 Hz), 5.59
(1H, d, J ) 9.2 Hz), 5.58 (1H, d, J ) 1.4 Hz), 5.52 (1H, br s),
5.45 (1H, br d, J ) 9.2 Hz), 4.81 (1H, dd, J ) 9.1, 6.9 Hz), 4.55
(1H, d, J ) 2.2 Hz), 3.35 (1H, dd, J ) 15.9, 4.0 Hz), 3.01 (4H,
s), 2.45 (1H, m), 2.32 (1H, dd, J ) 15.9, 2.6 Hz), 2.23 (1H, m),
2.18 (3H, s), 2.15 (3H, s), 2.04 (3H, s), 2.00 (3H, s), 1.77 (3H,
br s), 1.59 (3H, s), 1.49 (3H, s); 13C NMR (100 MHz, CDCl3) δ
ppm 171.1, 170.0, 169.2, 169.2, 142.2, 131.3, 122.4, 80.0, 77.2,
75.7, 73.5, 72.9, 72.1, 71.3, 62.2, 44.1, 42.0, 39.1, 35.2, 28.2,
24.0, 21.7, 21.0, 20.9, 20.6, 16.8, 10.6; ESIMS (m/z) 585 [M+
+
H] (22), 525 (45), 489 (100), 465 (33); HRESIMS (m/z) 585.2012
(calcd for C27H37O12S, M+ + H, 585.2006).
To a toluene (190 µL) solution of the above mesylate (11.5
mg, 19.7 µmol) was added 1,8-diazabicyclo[5.4.0]undec-7-ene
(14.7 µL, 98.5 µmol), and the mixture was stirred at 100 °C
for 5 h. To the reaction mixture was added acetic anhydride
(18.6 µL, 197 µmol), and then the reaction mixture was stirred
at room temperature for 46 h. The mixture was concentrated
under reduced pressure and then purified by Si gel column
chromatography (elution with n-hexane-EtOAc (4:3)) to give
9 (5.4 mg, 56% yield). The spectral data were identical with
those of natural 9.
Synthesis of Briaranolide J (10) from Briaranolide I
(9). To a cold (0 °C) solution of 9 (10.1 mg, 20.7 µmol) in
dichloromethane (200 µL) were added sodium hydrogenphos-
phate (7.3 mg, 51.7 µmol) and m-chloroperbenzoic acid (6.6 mg,
24.8 µmol) followed by stirring for 2.5 h. The mixture was
treated with dimethyl sulfide and allowed to warm slowly to
room temperature over 1 h. The reaction mixture was diluted
with diethyl ether, washed with water and brine, dried over
anhydrous magnesium sulfate, and concentrated under re-
duced pressure. The residue was purified by Si gel column
chromatography (elution with n-hexane-EtOAc (1:1)) to give
10 (7.3 mg, 70% yield). The spectral data were identical with
those of natural 10.
Synthesis of Bis-p-bromobenzoate 12 from Briarano-
lide F (6). To a methanol (3.5 mL) solution of 6 (101 mg, 175
µmol) was added lithium hydroxide monohydrate (7.3 mg, 175
µmol), and the mixture was stirred at room temperature for
43 h. The reaction mixture was neutralized with aqueous HCl
(1 M) and concentrated under reduced pressure. The residue
was purified by Si gel column chromatography (elution with
CHCl3-MeOH (14:1)) to give triol (24.0 mg, 32% yield):
24
colorless amorphous solid; [R]D +32.7° (c 0.9, CHCl3); IR
(neat) νmax 3457, 1782, 1755 cm-1; 1H NMR (400 MHz, CDCl3)
δ ppm 5.64 (1H, d, J ) 9.1 Hz), 5.35 (2H, br s), 5.31 (1H, d, J
) 9.1 Hz), 4.04 (1H, d, J ) 3.1 Hz), 3.52 (1H, dd, J ) 8.3, 6.8
Hz), 3.28 (1H, dd, J ) 14.6, 4.9 Hz), 3.27 (1H, br s), 3.06 (1H,
br s), 2.48 (1H, m), 2.12 (3H, s), 2.11 (1H, m), 2.03 (1H, dd, J
) 14.6, 2.6 Hz), 1.95 (3H, s), 1.68 (6H, br s), 1.44 (3H, s); 13C
NMR (100 MHz, CDCl3) δ ppm 171.5, 168.8, 143.8, 132.0,
121.3, 120.4, 77.2, 76.0, 73.8, 73.4, 72.6, 71.4, 62.1, 43.2, 42.6,
37.4, 32.1, 23.6, 22.3, 21.0, 17.9, 10.3; ESIMS (m/z) 423 [M+
+
Acknowledgment. This work was supported in part by
“High-Tech Research Center” Project for Private Universi-
ties: matching fund subsidy from Ministry of Education,
Culture, Sports, Science and Technology, 2002-2006.
H] (100), 405 (60), 203 (75); HRESIMS (m/z) 423.2004 (calcd
for C22H31O8, M+ + H, 423.2019).
To a pyridine (300 µL) solution of the above triol (14.5 mg,
34.3 µmol) was added p-bromobenzoyl chloride (37.7 mg, 172
µmol), and the mixture was stirred at room temperature for
1.5 h. The reaction mixture was diluted with diethyl ether and
washed with water, aqueous HCl (1 M), and brine. The organic
layer was dried over anhydrous magnesium sulfate and
Supporting Information Available: 1H and 13C NMR spectra
of new compounds (1-12) and crystallographic data of compounds 11
and 12. These materials are available free of charge via the Internet
at http://pubs.acs.org.

Epoxybriarane Diterpenoids from Briareum
Journal of Natural Products, 2005, Vol. 68, No. 9 1335
(11) Sheu, J.-H.; Sung, P.-J.; Cheng, M.-C.; Liu, H.-Y.; Fang, L.-S.;
Duh, C.-Y.; Chiang, M. Y. J. Nat. Prod. 1998, 61, 602-608. (b)
Rodr´ıguez, J.; Nieto, R. M.; Jime´nez, C. J. Nat. Prod. 1998, 61, 313-
317.
(12) Garcia, M.; Rodriguez, J.; Jimenez, C. J. Nat. Prod. 1999, 62, 257-
260.
(13) Recent examples: (a) Mitome, H.; Shirato, N.; Hoshino, A.; Miyaoka,
H.; Yamada, Y.; Soest, R. W. M. Steroids 2005, 70, 63-70. (b) Mitome,
H.; Shirato, N.; Miyaoka, H.; Yamada, Y.; Soest, R. W. M. J. Nat.
Prod. 2004, 67, 833-837. (c) Hoshino, A.; Mitome, H.; Miyaoka, H.;
Shintani, A.; Yamada, Y.; Soest, R. W. M. J. Nat. Prod. 2003, 66,
1600-1605.
(14) Flack, H. D.; Bernardinelli, G. Acta Crystallogr. 1999, A55, 908-
915, and references therein.
(15) The crystal structure has been deposited at the Cambridge Crystal-
lographic Data Centre and allocated the deposition number CCDC
265071.
(16) The crystal structure has been deposited at the Cambridge Crystal-
lographic Data Centre and allocated the deposition number CCDC
265072.
(17) Sung, P.-J.; Su, J.-H.; Wang, G.-H.; Lin, S.-F.; Duh, C.-Y.; Sheu, J.-
H. J. Nat. Prod. 1999, 62, 457-463.
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(8) Hendrickson, R. L.; CardellinaII, J. H. Tetrahedron 1986, 42, 6565-
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NP058037Q