Briarane-type diterpenoids from the Okinawan soft coral Pachyclavularia violacea

Article abstract of DOI:10.1021/np0580661

Four new briarane-type diterpenoids, pachyclavulides A (1), B (2), C (3), and D (4), were isolated from the Okinawan soft coral Pachyclavularia violacea. The structures of these compounds were elucidated on the basis of the results of spectroscopic analys

Full text of DOI:10.1021/np0580661

2
J. Nat. Prod. 2006, 69, 2-6
Full Papers
Briarane-Type Diterpenoids from the Okinawan Soft Coral PachyclaWularia Wiolacea
Junya Iwasaki, Hisanaka Ito,* Miwako Aoyagi, Yuki Sato, and Kazuo Iguchi*
School of Life Science, Tokyo UniVersity of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan
ReceiVed May 25, 2005
Four new briarane-type diterpenoids, pachyclavulides A (1), B (2), C (3), and D (4), were isolated from the Okinawan
soft coral PachyclaVularia Violacea. The structures of these compounds were elucidated on the basis of the results of
spectroscopic analysis. The absolute configuration of pachyclavulide A (1) was determined by the X-ray crystallographic
analysis of its p-bromobenzoyl ester.
Briarane-type diterpenoids have been noted owing to their
structural features and biological activity.1-3 The structures of these
diterpenoids are characterized by a highly oxygenated bicyclo[8.4.0]-
tetradecane skeleton frequently with a γ-lactone moiety. These
diterpenoids exhibited a variety of biological activities such as
antiinflammatory,4 cyctotoxicity,5 and reversal of multidrug resis-
tance.6,7 More than 300 briarane-type diterpenoids have been
reported so far mainly from gorgonian octocorals of the genera
Briareum, Ellisera, and Junicella and from sea pens of the genera
Stylatura, Pteroides, and Ptilosarcus. On the contrary, examples
of this type of diterpenoids from alcyonarian and stoloniferan soft
corals are limited. Only two reports8,9 were published on the
briarane-type diterpenoids from the stoloniferan soft coral of the
genus PachyclaVularia. Our continuing investigations10-12 on
Okinawan invertebrates have resulted in the isolation of four new
briarane-type diterpenoids, pachyclavulides A (1), B (2), C (3), and
D (4), from PachyclaVularia Violacea. This paper describes the
structural elucidation of these compounds.
as depicted in Figure 2. These partial structures were connected
by the HMBC analysis, leading to the gross structure of 1; the key
correlations observed in the HMBC spectrum are shown by broken
arrows in Figure 3.
The Z configuration of the trisubstituted double bond at C-5 was
determined by the NOE correlation between the olefinic methyl
(H-16) and the olefinic proton (H-6), as shown by the broken arrow
in Figure 4. The relative stereochemistry of the 10 chiral centers
in 1 was deduced from the analysis of NOE correlations with
suppoting information from vicinal coupling constants (Table 1).
The absolute stereochemistry of 1 was determined by X-ray
crystallographic analysis of p-bromobenzoate 5, which was prepared
by treatment of 1 with p-bromobenzoic acid in the presence of EDC
and DMAP, as shown in Figure 5.
The molecular formula of pachyclavulide B (2) was found to be
C26H34O10 by HRESIMS and 13C NMR data. The IR spectrum
showed absorptions at 3416 cm-1 due to hydroxyl groups and at
1770, 1732, 1251, and 1225 cm-1 due to ester groups. The 13C
NMR spectrum (Table 1) disclosed the signals due to six methyls,
one sp3 methylene, one sp3 oxymethylene, two sp3 methines, four
sp3 oxymethines, one sp3 quaternary carbon, one sp3 quaternary
carbon bearing an oxygen function, four sp2 methines, two sp2
quaternary carbons, and four carbonyl carbons. The low-field
carbonyl carbon at δC 176.1 (C), coupled with the IR absorption at
1770 cm-1, suggested the presence of a γ-lactone moiety in 2. The
1H NMR (Table 1) showed the signals due to one secondary methyl,
one tertiary methyl, one olefinic methyl, three acetoxyl methyls,
one oxymethylene, four oxymethines, and four olefinic protons.
These spectral data, coupled with the degrees of unsaturation (10),
suggested that compound 2 was a tricyclic diterpenoid with a
γ-lactone, three acetoxyl groups, a hydroxylmethyl group, and three
olefins.
The isolation and purifucation were carried out as described in
the Experimental Section.
Results and Discussion
The molecular formula of pachyclavulide A (1) was found to be
C26H38O10 by HRESIMS and 13C NMR data. The IR spectrum
showed absorptions at 3442 cm-1 due to hydroxyl groups and at
1775, 1745, 1734, 1260, and 1217 cm-1 due to ester groups. The
13C NMR spectrum (Table 1) disclosed the signals due to seven
methyls, three sp3 methylenes, three sp3 methines, five sp3 oxyme-
thines, one sp3 quaternary carbon, one sp3 quaternary carbon bearing
an oxygen function, two sp2 carbons, and four carbonyl carbons.
The low-field carbonyl carbon [δC 177.0 (C-19)], coupled with the
IR absorption at 1775 cm-1, suggested the presence of a γ-lacone
1
moiety in 1. The H NMR spectrum (Table 1) showed the signals
due to two secondary methyls, one tertiary methyl, one olefinic
methyl, three acetoxyl methyls, five oxymethines, and one olefinic
proton. These spectral data, coupled with the degrees of unsaturation
(8), suggested that compound 1 is a tricyclic diterpenoid with a
γ-lactone, three acetoxyl groups, and a trisubstituted olefin.
The HMQC analysis revealed the assignment of each direct C-H
The HMQC analysis revealed the assignment of each direct C-H
bonding in 2 as summarized in Table 1. The skeletal structure of
1
2 was deduced from H-1H COSY and HMBC correlations as
shown in Figure 6.
The Z configuration of the disubstituted double bond at C-3 was
determined by the proton coupling constant (J ) 10.9 Hz) between
the olefinic protons H-3 and H-4. The E configuration of the
trisubstituted double bond at C-5 was demonstrated by the NOE
correlation between the olefinic proton (H-6) and the olefinic
hydroxymethyl (H-16), as shown by the broken arrow in Figure 7.
The relative stereochemistry of the eight chiral centers of 2 was
also deduced by the analysis of NOE correlations. The absolute
1
bonding in 1 as summarized in Table 1. The H-1H correlations
obtained from the 1H-1H COSY exhibited partial structures a-d,
* To whom correspondence should be addressed. Tel: +81-426-76-5473.
Fax: +81-426-76-7282. E-mail: itohisa@ls.toyaku.ac.jp (H.I.). Tel: +81-
426-76-7273. Fax: +81-426-76-7282. E-mail: onocerin@ls.toyaku.ac.jp
(K.I.).
10.1021/np0580661 CCC: $33.50
© 2006 American Chemical Society and American Society of Pharmacognosy
Published on Web 12/16/2005

Briarane-Type Diterpenoids from PachyclaVularia
Journal of Natural Products, 2006, Vol. 69, No. 1 3
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Table 1. 13C and H NMR Data of Compounds 1 and 2a
1
2
no.
δC
δH
no.
δC
δH
1
2
3
45.3 (C)
76.0 (CH)
31.1 (CH2)
1
2
3
4
5
6
7
8
43.5 (C)
76.0 (CH)
131.8 (CH)
128.6 (CH)
146.2 (C)
122.4 (CH)
80.0 (CH)
81.1 (C)
69.8 (CH)
39.7 (CH)
134.0 (C)
120.6 (CH)
26.6 (CH2)
4.92 (1H, d, 6.4)
1.51 (1H, m)
2.76 (1H, dt, 4.8, 15.1)
2.45 (1H, m)
5.43 (1H, d, 9.8)
5.73 (1H, dd, 9.8, 10.9)
6.28 (1H, d, 10.9)
4
28.8 (CH2)
2.00 (1H, m)
5.79 (1H, dd, 1.4, 8.9)
5.21 (1H, d, 8.9)
5
6
7
8
146.8 (C)
117.7 (CH)
79.0 (CH)
82.0 (C)
5.38 (1H, d, 9.7)
5.16 (1H, d, 9.7)
9
5.87 (1H, d, 4.9)
3.05 (1H, br s)
10
11
12
13
9
75.3 (CH)
37.9 (CH)
44.2 (CH)
66.9 (CH)
28.9 (CH2)
77.2 (CH)
15.1 (CH3)
27.6 (CH3)
43.5 (CH)
6.5 (CH3)
177.0 (C)
9.0 (CH3)
170.6 (C)
21.4 (CH3)
169.0 (C)
21.7 (CH3)
170.6 (C)
21.2 (CH3)
5.26 (1H, br s)
2.56 (1H, br s)
2.04 (1H, m)
3.98 (1H, td, 4.4, 11.3)
1.75 (2H, m)
4.74 (1H, br s)
1.067 (3H, s)
2.02 (3H, br s)
2.43 (1H, q, 7.1)
1.17 (3H, d, 7.1)
10
11
12
13
14
15
16
17
18
19
20
Acb
5.44 (1H, br s)
1.97 (1H, t, 18.0)
2.29 (1H, br d, 19.1)
4.98 (1H, br s)
14
15
16
72.8 (CH)
14.8 (CH3)
63.9 (CH2)
1.01 (3H, s)
4.26 (1H, d, 14.8)
4.42 (1H, d, 14.8)
2.43 (1H, q, 7.2)
1.29 (3H, d, 7.2)
17
18
19
44.4 (CH)
7.5 (CH3)
177.0 (C)
24.6 (CH3)
170.6 (C)
21.36 (CH3)
169.8 (C)
21.7 (CH3)
169.8 (C)
21.3 (CH3)
1.074 (3H, d, 7.5)
1.98 (3H, s)
20
1.95 (3H, br s)
2.01 (3H, s)
2.16 (3H, s)
Acb
Acc
Acd
OH
Acc
Acd
2.18 (3H, s)
1.94 (3H, s)
3.50 (1H, br s)
1.98 (3H, s)
3.11 (1H, s)
3.25 (1H, br s)
OH
OH
1
1
a 13C NMR: 125 MHz in CDCl3. H NMR: 500 MHz in CDCl3. J in Hz. Assignments of the 13C and H signals were made on the basis of
HMQC. b,c,d The positions of these acetoxyl groups are at C-2 for b, C-9 for c, and C-14 for d.
Figure 1. Structures of new diterpenoids.
Figure 2. Partial structures, 1H NMR data, and 1H-1H correlations
(broken arrows) of pachyclavulide A (1).
stereochemistry of 2 must be the same as that of 1 present in the
same soft coral.
The molecular formula of pachyclavulide C (3) was found to be
C28H36O11 by HRESIMS and 13C NMR data. The 13C and 1H NMR
data of 3 (Table 2) were very similar to those of 2, except for the
signals due to a primary acetoxyl group instead of the primary
hydroxyl group in 2, indicating that compound 3 was the corre-
sponding tetraacetate of triacetate 2. This was confirmed by the
chemical conversion. Acetylation of 2 with acetic anhydride in
pyridine afforded an acetate, the 1H NMR spectrum and [R]D value
of which were identical with those of 3.
The molecular formula of pachyclavulide D (4), containing a
chlorine atom, was found to be C24H29ClO10 by HRESIMS and
13C NMR data. The IR spectrum showed absorptions at 3300 cm-1
due to hydroxyl groups, at 1779, 1747, and 1210 cm-1 due to ester
groups, and at 1698 cm-1 due to a conjugated carbonyl group. The
13C NMR spectrum (Table 2) disclosed the signals due to five
methyls, eight sp3 methines, two sp3 quaternary carbons, one sp2
methylene, two sp2 methines, one sp2 quaternary carbon, and four
carbonyl carbons. The low-field ester carbonyl carbon [δC 174.3

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Journal of Natural Products, 2006, Vol. 69, No. 1
Iwasaki et al.
1
Figure 6. Gross structure, H-1H correlations (bold lines), and
1
Figure 3. Gross structure, H-1H correlations (bold lines), and
key HMBC correlations (broken arrows) of pachyclavulide B (2).
key HMBC correlations (broken arrows) of pachyclavulide A (1).
Figure 7. Key NOE correlations (broken arrows) and possible
conformation for pachyclavulide B (2).
Figure 4. Key NOE correlations (broken arrows) and possible
conformation for pachyclavulide A (1).
obtained from the 1H-1H COSY exhibited partial structures h-k.
These partial structures were connected by HMBC correlations, as
shown by broken arrows in Figure 8, to afford the gross structure
for 4. The relative stereochemistry of the 11 chiral centers in 4
was deduced by the NOE analysis (Figure 9). The absolute
stereochemistry of 4 must be the same as that of 1 present in the
same soft coral.
Experimental Section
General Experimental Procedures. Optical rotations were mea-
sured with a JASCO DIP-370 automatic polarimeter. IR spectra were
recorded with a Perkin-Elmer FT-IR 1600 spectrophotometer. All NMR
spectra were recorded with a Bruker DRX-500 (1H, 500 MHz; 13C,
125 MHz) spectrometer. 1H-1H COSY, NOESY, HMQC, and HMBC
spectra were measured using standard Bruker pulse sequences. Chemical
shifts are given on a δ (ppm) scale with CHCl3 (1H, 7.26 ppm) and
CDCl3 (13C, 77.0 ppm) as the internal standard. Mass spectra were taken
with a Micromass LCT spectrometer.
Animal Material. The soft coral PachyclaVularia Violacea (order
Stolonifera, class Clavularidae) was collected from a coral reef off
Ishigaki Island, Okinawa Prefecture, Japan, in September 1995. A
voucher specimen has been deposited at Tokyo University of Pharmacy
and Life Science, Tokyo, Japan.
Figure 5. Perspective view (ORTEP) of the molecule of compound
5.
(C)], coupled with the IR absorption at 1779 cm-1, suggested the
presence of a γ-lactone moiety in 4. On the other hand, the high-
field ketonic carbonyl carbon [δC 198.7 (C)] suggested that the
carbonyl group was conjugated with a carbon-carbon double bond.
Extraction and Isolation. Wet specimens (2.3 kg) of the soft coral
collected in 1995 were extracted with MeOH. The MeOH extract (103
g) was partitioned between EtOAc and H2O to obtain an EtOAc-soluble
portion (41.0 g). A part (1.98 g) of the EtOAc-soluble portion was
chromatographed on a silica gel column. Elution with hexane-EtOAc
(1:1) afforded five fractions. The fourth fraction (278 mg) was subjected
to normal-phase HPLC [hexane-2-propanol (3:1)] to afford four
fractions. Further repeated purification of each fraction using normal-
and reversed-phase HPLCs afforded pachyclavulide C (3) (4.0 mg) from
the first fraction (16.1 mg) and pachyclavulides A (1) (7.1 mg), B (2)
(3.8 mg), and D (4) (1.9 mg) from the fourth fraction (278 mg).
1
The H NMR spectrum (Table 2) showed the signals due to one
secondary methyl, two tertiary methyls, two acetoxyl methyls, one
methine bearing a chlorine atom, five oxymethines, one exometh-
ylene, and two olefinic methines. These spectral data, coupled with
the degrees of unsaturation (10), suggested that compound 4 is a
tetracyclic diterpenoid with a γ-lactone, an R,â-unsaturated ketone,
an epoxide, an exocyclic olefin, and two acetoxyl groups.
Pachyclavulide A (1): colorless amorphous solid; [R]25 -4.7 (c
The HMQC analysis revealed the assignment of each direct C-H
D
1
bonding in 4 as summarized in Table 2. The H-1H correlations
0.58, CHCl3); IR νmax (film) 3442, 1775, 1745, 1734, 1260, 1217 cm-1
;

Briarane-Type Diterpenoids from PachyclaVularia
Journal of Natural Products, 2006, Vol. 69, No. 1 5
1
Table 2. 13C and H NMR Data of Compounds 3 and 4a
3
4
no.
δC
43.4 (C)
δH
no.
δC
43.4 (C)
δH
1
1
2
3
4
5
6
7
8
74.6 (CH)
132.9 (CH)
126.7 (CH)
141.6 (C)
120.8 (CH)
79.7 (CH)
81.1 (C)
5.45 (1H, d, 9.4)
5.76 (1H, dd, 9.4, 10.9)
6.22 (1H, d, 10.9)
2
3
4
5
6
7
8
75.5 (CH)
59.5 (CH)
58.3 (CH)
133.8 (C)
59.8 (CH)
77.8 (CH)
82.1 (C)
4.85 (1H, d, 9.0)
3.49 (1H, dd, 3.7, 8.9)
3.66 (1H, d, 3.7)
5.58 (1H, d, 8.7)
5.20 (1H, d, 8.7)
5.19 (1H, d, 3.5)
5.06 (1H, d, 3.5)
9
69.7 (CH)
39.8 (CH)
133.8 (C)
120.8 (CH)
26.7 (CH2)
5.87 (1H, d, 4.8)
3.00 (1H, br s)
9
69.2 (CH)
43.3 (CH)
75.8 (C)
198.7 (C)
121.7 (CH)
155.4(CH)
14.6 (CH3)
118.9 (CH2)
5.85 (1H, d, 6.4)
2.77 (1H, d, 6.4)
10
11
12
13
10
11
12
13
14
15
16
5.45 (1H, d, 9.4)
2.00 (1H, m)
2.28 (1H, br d, 19.1)
4.97 (1H, br s)
1.00 (3H, s)
4.60 (1H, d, 15.8)
17
2.44 (1H, q, 7.2)
1.28 (3H, d, 7.2)
6.09 (1H, d, 10.6)
6.53 (1H, d, 10.6)
1.01 (3H, s)
5.65 (1H, d, 2.1)
6.02 (1H, d, 2.1)
14
15
16
72.6 (CH2)
14.8 (CH3)
63.7 (CH2)
5.20 (1H, d, 15.8)
44.4 (CH)
7.5 (CH3)
175.9 (C)
24.5 (CH3)
169.4 (C)
21.2 (CH3)
169.8 (C)
21.6 (CH3)
171.1 (C)
21.3 (CH3)
171.1 (C)
21.3 (CH3)
46.3 (CH)
18
19
2.47 (1H, q, 7.1)
6.8 (CH3)
174.3 (C)
25.3 (CH3)
169.4 (C)
20.9 (CH3)
169.3 (C)
17
18
19
1.26 (3H, d, 7.1)
1.49 (3H, br s)
2.22 (3H, s)
20
20
1.95 (3H, br s)
1.98 (3H, s)
2.16 (3H, s)
2.00 (3H, s)
2.13 (3H, s)
Acb
Acb
Acc
Acc
Acd
Ace
21.8 (CH3)
21.7 (CH3)
2.28 (3H, s)
2.16 (3H, s)
4.90 (1H, s)
5.47 (1H, br s)
OH
OH
1
1
a 13C NMR: 125 MHz in CDCl3. H NMR: 500 MHz in CDCl3. J in Hz. Assignments of the 13C and H signals were made on the basis of
HMQC. b,c,d The positions of these acetoxyl groups are at C-2 for b, C-9 for c, and C-14 for d.
Figure 9. Key NOE correlations (broken arrows) and possible
conformation for pachyclavulide D (4).
(48 mg), and DMAP (2 mg), and the mixture was stirred at room
temperature for 36 h. The reaction mixture was concentrated under
reduced pressure, and the residue was purified by silica gel column
chromatography to give p-bromobenzoate 5 (14.5 mg) in quantitative
1
Figure 8. Gross structure, H-1H correlations (bold lines), and
yield.
p-Bromobenzoate 5: colorless prisms; 1H NMR (500 MHz, CDCl3,
δ ppm) 1.16 (3H, s), 1.22 (3H, d, J ) 7.1 Hz), 1.23 (3H, d, J ) 7.7
Hz), 2.00 (3H, s), 2.08 (3H, s), 2.09 (3H, br s), 2.23 (3H, s), 2.34 (1H,
m), 2.45 (1H, q, J ) 7.1 Hz), 2.66 (1H, dd, J ) 2.5, 4.9 Hz), 2.80 (1H,
dt, J ) 5.6, 15.2 Hz), 4.88 (1H, m), 4.99 (1H, d, J ) 6.9 Hz), 5.21
(1H, d, J ) 9.7 Hz), 5.32 (1H, d, J ) 2.5 Hz), 5.33-5.41 (2H, m),
7.58 (2H, d, J ) 8.6 Hz), 7.85 (2H, d, J ) 8.6 Hz).
key HMBC correlations (broken arrows) of pachyclavulide D (4).
13C and H NMR, see Table 1; HRESIMS m/z 511.2539 [M + H]+
1
(calcd for C26H39O10, 511.2534).
Pachyclavulide B (2): colorless amorphous solid; [R]25 -2.9 (c
D
0.27, CHCl3); IR νmax (film) 3416, 1770, 1732, 1251, 1225 cm-1
;
13C
and 1H NMR, see Table 1; HRESIMS m/z 529.2031 [M + Na]+ (calcd
for C26H34O10Na, 529.2050).
Acetylation of Pachyclavulide B (2). To a solution of 2 (0.5 mg)
in CH2Cl2 (0.3 mL) were added pyridine (5 drops) and acetic anhydride
(5 drops). The mixture was stirred for 1 h at room temperature. After
addition of excess H2O the mixture was extracted with ether, and the
ethereal layer was successively washed with aqueous NaHCO3, H2O,
aqueous CuSO4, H2O, and saturated aqueous NaCl, dried over
anhydrous MgSO4, and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography to give an
acetate, the 1H NMR spectrum of which was identical with that of
pachyclavulide C (3). The optical rotation data [[R]25D -20.0 (c 0.04,
CHCl3)] of the acetate also coincided with that of 3.
Pachyclavulide C (3): colorless amorphous solid; [R]25 -19.8 (c
D
0.81, CHCl3); IR νmax (film) 3446, 1770, 1731, 1714, 876 cm-1
;
13C
and 1H NMR, see Table 2; HRESIMS m/z 571.2155 [M + Na]+ (calcd
for C28H36O11Na, 571.2173).
Pachyclavulide D (4): colorless amorphous solid; [R]25 -30 (c
D
0.04, CHCl3); IR νmax (film) 3300, 1779, 1747, 1698, 1210 cm-1
;
13C
and 1H NMR, see Table 2; HRESIMS m/z 513.1531 [M + H]+ (calcd
for C24H3035ClO10, 513.1528).
Esterification of Pachyclavulide A (1). To a solution of 1 (10 mg)
in CH2Cl2 (1.0 mL) were added p-bromobenzoic acid (40 mg), EDC

6
Journal of Natural Products, 2006, Vol. 69, No. 1
Iwasaki et al.
(3) Blunt, J. W.; Copp, B. R.; Munro, M. H. G.; Northcote, P. T.; Prinseo,
M. R. Nat. Prod. Rep. 2004, 21. 1-49, and the previous paper in
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X-ray Crystal Structure Determination of 5. A colorless prism
of 5 was obtained by recrystallization from hexane-EtOAc (5:1). A
single crystal with dimensions of 0.43 × 0.33 × 0.25 mm was used
for X-ray diffraction studies on a Mac Science DIP2020 diffractometer
employing graphite-monochromated Mo KR radiation (λ ) 0.71073
Å). The structure was solved by a direct method using SIR9713 in the
maXus program system and refined by SHELXL9714 using 11 077
reflections [I > 2.00σ(I)] for 884 parameters. The final R value is 0.035.
Crystal Data: 2(C33H41BrO11)‚C4H8O2‚2(H2O), monoclinic with
space group P21, with a ) 11.1960(5) Å, b ) 25.7150(5) Å, c )
13.8270(6) Å, V ) 3643.1 (2) Å, and Z ) 2. Crystallographic data for
the structure reported in this paper have been deposited with Cambridge
Crystallographic Data Centre (deposition number CCDC 284180).
Copies of the data can be obtained, free of charge, on application to
the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
+44-(0)1223-336033 or e-mail: deposite@ccdc.cam.ac.uk).
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Andersen, R. J. Tetrahedron 2000, 56, 9031-9037.
(10) Iguchi, K.; Fukaya, T.; Takahashi, H.; Watanabe, K. J. Org. Chem.
2004, 69, 4351-4355.
Acknowledgment. The authors express appreciation to H. Fukaya,
Tokyo University of Pharmacy and Life Science, for conducting the
X-ray crystallographic analysis.
(11) Iguchi, K.; Fukaya, T.; Yasumoto, A.; Watanabe, K. J. Nat. Prod.
2004, 67, 577-583.
1
Supporting Information Available: Copies of H and 13C NMR
(12) Watanabe, K.; Sekine, M.; Iguchi, K. J. Nat. Prod. 2003, 66, 1434-
1440.
spectra of pachyclavulides A-D (1-4). These materials are available
free of charge via the Internet at http://pubs.acs.org.
(13) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G.; Spagna, R. J. Appl.
Crystallogr. 1999, 32, 115-119.
(14) Sheldrick, G. M. SHELXL97, Program for the Refinement of Crystal
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References and Notes
(1) Sung, P.-J.; Sheu, J.-H.; Xu, J.-P. Heterocycles 2002, 57, 535-579.
(2) Faulkner, D. J. Nat. Prod. Rep. 2002, 19, 1-48, and previous papers
in this series.
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