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Tetrahedron 65 (2009) 6029-6033 
ELSEVIER 
Contents lists available at ScienceDirect 
Tetrahedron 
journal homepage: www.elsevier.com/locate/tet 
Leptogorgolide, a biogenetically interesting 1,4-diketo-cembranoid that reinforces 
the oxidation profile of C-18 as taxonomical marker for octocorals 
Ana R. Diaz-Marrero3*, Gina Porras3, Mercedes Cueto3, Luis D'Crozbc, Manuel Lorenzod, 
Aurelio San-Martin e, J. Darias a 
a
 Institute de Productos Naturales y Agrobiologia del CSIC, Avda Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife, Spain 
bSmithsonian Tropical Research Institute, P.O. Box 2072, Balboa, Panama 
c
 Departamento de Biologia Marina y Limnologia. Estafeta Universitaria, Universidad de Panama, Panama 
d
 Universidad de Magallanes, Avenida Bulnes 01855, Punta Arenas, Chile 
E
 Universidad de Chile, Departamento de Quimica, Santiago de Chile, Chile 
ARTICLE    INFO 
Article history: 
Received 22 April 2009 
Received in revised form 21 May 2009 
Accepted 26 May 2009 
Available online 29 May 2009 
Keywords: 
Leptogorgia 
Leptogorgolide 
1,4-Diketo-cembranoid 
ABSTRACT 
The cembranoid 1 and the furanocembranolides 2-4 along with the known pukalide were isolated from 
Leptogorgia sp. and their structures determined spectroscopically. The 1,4-diketo-cembranoid 1 follows 
an oxidation pattern of C-18 that reinforces the concept of oxidation profile of C-18 as taxonomical 
marker for octocorals. The co-occurrence within a species of furanocembranolide/l,4-diketo-cembranoid 
congeners 1/2-4 raises the question about which one is the biogenetic precursor. A biogenetic pathway is 
proposed. 
? 2009 Elsevier Ltd. All rights reserved. 
1. Introduction 
Octocorals of the genera Pseudopterogorgia,Alcyonium, Gersemia, 
Lophogorgia, Leptogorgia, and Sinularia have the ability to bio- 
synthesize highly oxygenated diterpenoids based on a 14-mem- 
bered carbocyclic cembrane skeleton1 into which a substituted furan 
ring and a y-lactone subunit are embedded. The oxidative cleavage 
of the furan ring may lead to a 1,4-diketo-derivative and naturally 
occurring metabolites with this feature are frequently found, 
mainly in species of genera Pseudopterogorgia, Alcyonium, Gerse- 
mia, and Sinularia. However, the co-occurrence of both fur- 
anocembranolides and their 1,4-diketo-cembranoid equivalents 
within a species raises the question about which one is the bio- 
genetic precursor. 
The search for marine natural products produced by benthic 
organisms from both sides of the Isthmus of Panama2 prompted us 
to study the eastern Pacific octocoral Leptogorgia sp. In this paper 
we report on the structures of four new cembranoids 1-4 along 
with the known compound pukalide,3 isolated from this species. In 
a previous paper, based on a survey on marine furanocem- 
branolides, we introduced the concept of genus-specific oxidation by 
Corresponding author. Tel.: +34 922 252 144: fax: +34 922 260 135. 
E-mail address: ardiaz@ipna.csic.es (A.R. Diaz-Marrero). 
which these metabolites could be divided into four classes 
according to the oxidation degree of their C-18: class A (Me), class B 
(CHO), class C (COOH), and class D (COOMe).4 This classification 
provides a criterion as taxonomical marker for octocorals. In this 
work, for the first time a 1,4-diketo-cembranoid 1 with an oxidized 
C-18 as a methyl ester has been discovered in Leptogorgia. Thus, the 
occurrence in Leptogorgia of compound 1 and the related fur- 
anocembranolide equivalents 2-4 suggested that the 1,4-diketo- 
cembranoid congeners may follow a parallel genus-dependent C-18 
specific oxidation. 
A new analysis of furanocembranoids and 1,4-diketo-cem- 
branoids isolated from species of the aforementioned six genus are 
summarized in Table 1. The following features were observable: (1) 
species of genus Pseudopterogorgia biosynthesize furanocem- 
branolides of classes A, C, and D as well as 1,4-diketo-cembranoid 
congeners of class A (i.e., bipinnatin P) and class D (bipinnatin Q, 
la)5 and a l,4-diketo-nor-C-18-cembranoid (gorgiacerolide);6 (2) 
species of genus Alcyonium and Gersemia exclusively biosynthesize 
1,4-diketo-cembranoids and furanocembranolides of class A; (3) no 
1,4-diketo-cembranoids of class B, which are to be expected for 
species of genus Lophogorgia and Leptogorgia, have been described; 
(4) species of genus Sinularia biosynthesize furanocembranolides 
and 1,4-diketo-cembranoids of class D. This genus is also specially 
rich in l,4-diketo-nor-C-18-cembranolides. Table 1 indicates that C- 
18 of 1,4-diketo-cembranoids, as well as their furanocembranoid 
0040-4020/$ - see front matter ? 2009 Elsevier Ltd. All rights reserved. 
doi:10.1016/j.tet.2009.05.068 
6030 A.R. Diaz-Marrero et al. / Tetrahedron 65 (2009) 6023-6033 
Table 1 
Correlation genus/class A- -Da of cembranoids and nor-C-18-cembranoids 
Genus Furanocembranoids 1,4-Diketo-cembranoids 
Pseudopterogorgia 
Alcyonium 
A, C,D 
A 
A, D, nor-C-18 
A 
Gersemia A A 
Lophogorgia 
Leptogorgia 
Sinularia 
B 
B, D 
0 
Unknown 
D 
D, nor-C-18 
a
 Class indicates the type of functionality of C-18: class A (Me); class B (CHO); class 
C (COOH); class D (COOMe). 
congeners follow an identical oxidation pattern, which reinforces 
the concept of genus-specific oxidation as taxonomical marker for 
octocorals. 
Leptogorgolide 1 is oxidized at C-18 (class D) as expected for 
Leptogorgia cembranoids. This and the above facts suggested that 
1,4-diketo-cembranoids may follow an oxidation pattern at C-18 
like their related furanocembranoids, thus reinforcing the concept 
of genus-specific oxidation as taxonomical marker for octocorals. 
2. Results and discussion 
Leptogorgolide 1 was an unstable colorless oil [ajo0 -61 (c 0.23, 
CH2CI2). Its EIMS showed a peak at 404.1457, which corresponds to 
the empirical formula C2iH2408 [M-CH3COOH]+ (HREIMS). Ab- 
sorption for carbonyl groups at 1785, 1765, and 1740 cnrr1 were 
observed in the 1R spectrum. The 13C NMR and DEPT spectra of 1 
(Table 2) showed the presence of 23 carbon signals assigned to 
4xCH] (one methoxy group, and one from an acetyl group), 5xCH2 
(one olefinic), 6xCH and eight quaternary carbons (two ketones, 
three carboxyls and one olefinic). 1H and 13C NMR data were very 
similar to those of bipinnatin Q,5 particularly the chemical shifts for 
the carbons implied in the 1,4-dicarbonyl moiety of the molecule. 
Connectivity information obtained from COSY, HSQC, and HMBC 
experiments unambiguously determined the planar structure of 
compound 1 as a 1,4-diketo cembranoid containing a C5-C8-oxane 
ring, a C10-C20-epoxylactone, and an acetate group at C-13. 
The relative stereochemistry of compound 1 was deduced by the 
study of NOESY experiments and coupling constants. NOE corre- 
lations of H3-I9 with H-5 as well as the correlation of H-5 with H-4 
indicated that H-4, H-5, and Me-19 are on the same face of the 
molecule. A dihedral angle of 95? for H-10/H-11 calculated for the 
energy-minimized7 conformation of 1, Figure 2, proved to be in 
good agreement with the absence of coupling constant for H-ll (<5 
4.25, s) (Table 2), and confirms the relative stereochemistry of C-10 
and C-ll as represented in 1. On the other hand, the NOE observed 
between H-ll and H-13 and between H-13 and HI as well as thej 
values of H-13 (dd, 9.1 and 5.4 Hz) fixed the relative configuration 
of the acetyl group and the epoxide ring as shown, thus establishing 
the whole relative stereochemistry of 1. 
Leptodiol 2 was a colorless oil [a]o0 +44 (c 0.41, CH2CI2) with 
a mass of 464.1666 corresponding to an elemental composition of 
C23H28O10. The NMR data of 2 (Table 2) resemble those of lophodiol 
A,8 2a, Figure 1, with the primary difference being an methyl ester 
substituent at C-4 (<5H 3.78 s, i5c 51.5 and <5c 163.8 ppm) instead of the 
aldehyde group of compound 2a. The planar structure of compound 2 
was confirmed by, COSY, HSQC, and HMBC experiments. 
Acetate of leptodiol 3 was isolated as an oil [a]o0 +27 (c 0.49, 
CH2C12). NMR data coupled with a molecular ion at mjz 506.1809 
(HREIMS) suggested a molecular formula o^^H^oO,, indicating 11 
degrees of unsaturation. Compound 3 was verified as the acetate 
derivative of leptodiol 2, as was corroborated via chemical trans- 
formation. Acetylation of 2 produced a compound whose :H NMR 
spectrum displays signals that exactly reproduce those obtained for 
the natural product. 
Comparison of the coupling constants of H2-9, H-10, H-ll, and 
H-13 of 2 and 3 with those of lophodiol A 2a and its acetate 3a, 
Table 2 
NMR data of compounds 1-4 [500 MHz, < ppm, (/) Hz, CDC3] 
No. Leptogorgolide 1 Leptodiol 2 Leptodiol acetate 3 8-epi-Lopholide 4 
<5H <5c <5H <5c 6? <5c 5H <5c 
1 3.06 m 38.9 3.20 br s 37.6 3.26 br s 37.8 2.60 (overlapped) 40.8 
2 2.58 m 
2.67 dd (12.9, 8.2) 
45.4 3.00 m 32.7 3.09 dd (17.0,10.4) 
3.01 dd (17.0,4.1) 
32.6 3.32 dd (14.8,11.7) 
3.09 dd (14.8, 3.2) 
30.9 
3 202.4 159.8 160.1 161.5 
4 3.92 d (2.5) 60.8 115.0 115.5 115.3 
5 4.26 d (2.5) 76.4 6.62 s 108.9 6.63 s 109.8 6.78 s 112.7 
6 ? 211.1 152.6 149.0 147.4 
7 2.64 d (18.0) 
2.51 d (18.3) 
50.4 5.12 br s 73.5 6.14 s 74.3 3.76 s 57.3 
8 80.0 73.9 73.5 59.4 
9 2.27 m 
2.56 m 
41.8 1.61 dd (14.5, 8.8) 
1.68 dd (14.5, 6,9) 
41.1 1.61 dd (14.8, 9.2) 
1.75 dd (14.8, 6.9) 
41.4 2.60 dd (14.5, 4.7) 
1.71 m (overlapped) 
35.8 
10 4.76 dd (6.0,2.2) 77.5 4.78 dd (8.7. 7.2) 74.7 4.78 dd (8.8, 6.9) 74.6 4.55 dd (12.6,4.7) 75.0 
11 4.25 s 66.6 4.24 br s 63.3 4.09 m 63.0 3.66 br s 62.9 
12 ? 60.3 59.0 59.0 58.6 
13 5.16 dd (9.1.5.4) 67.9 4.94 dd (6.6, 2.8) 69.2 4.95 dd (7.3, 2.8) 69.2 4.95 dd (6.9. 6.6) 65.8 
14 2.04 m 
2.29 m 
34.5 1.76 d (14.8) 
2.32 m 
33.0 1.70 m 
2.37 m 
33.0 2.22 ddd (14.8, 7.6, 7.6) 
1.71 m (overlapped) 
34.3 
15 147.0 147.3 147.2 146.3 
16 4.63 br s 
4.74 dd (1.3,1.3) 
111.6 4.81 s 
4.79 s 
110.9 4.83 br s 111.1 4.80 s 
4.73 s 
110.5 
17 1.72 s 19.2 1.80 s 20.7 1.82 s 20.6 1.80 s 21.6 
18 167.5 163.8 163.5 163.1 
19 1.48 s 26.0 1.38 s 22.7 1.40 s 23.2 1.52 s 21.7 
20 168.7 168.8 167.9 167.6 
21 3.75 s 52.7 3.78 s 51.5 3.79 s 51.6 3.83 s 51.7 
22 169.8 170.6 170.4 169.7 
23 2.08 s 20.9 2.05 s 20.6 2.06 s 20.6 2.01 s 20.7 
24 169.7 
25 2.16 s 20.9 
A.R. Diaz-Marrero et al. / Tetrahedron 65 (2003) 6029-6033 6031 
Table 3 
'H NMR A<5 (I5R-(5S) values (CDC13, ppm, recorded at 500 MHz) of the diastereomeric 
MPA esters 2b and 2c 
2:   R, = COOMe; R2 = H 
1a, bipinnatin Q: R = CHO    2a, lophodiol A: R, = CHO; R2 = H 
2b: R, = COOMe; R2 = (RJ-MPA 
2c: R, = COOMe; R2 = (SJ-MPA 
3:   R-, = COOMe; R2 = COMe 
3a: R, = CHO; R2 = COMe 
R 
OCOMe 
4:   R = COOMe 5, lopholide:  R = COOMe 
4a, 8-epi-lophotoxin: R = CHO     6, lophotoxin: R - CHO 
Figure 1. Cembranolides 1-4 and related known cembranoids. 
respectively, indicates that 2 and 3 must possess the same relative 
sterochemistry as lophodiol A, Table SI (Supplementary data). The 
relative configuration at C-7 and C-8 of 2 and 3 was corroborated by 
the NOE observed between H-7 with H3-I9 and H-5, Figure 2. 
Figure 2. Selected NOEs of compounds 1-4. 
The absolute configuration of 2 was established by derivatization 
with (R)- and (S)-a-methoxy-a-phenylacetic acids (MPA). NMR anal- 
ysis9 of the A<5 values for the two MPA esters 2b and 2c gave clear 
evidence to assign the absolute stereochemistry at C-7 as S, Table 3. 
Thus, this information allowed to establish the absolute configuration 
of leptodiol 2 as 1R,7S,8S,10S,11S,12S,13R. 
OR A?y 
H-5 
Me-19 
H-10 
6.58 
1.00 
4.38 
6.41 
1.32 
4.63 
+0.17 
-0.32 
-0.25 
8-epi-Lopholide 4 was isolated as a colorless oil [<X]D -22 (c 
0.41, CH2CI2). Its HREIMS exhibited a molecular ion peak at m/z 
446.1546, consistent with the molecular formula C23H26O9. The 
planar structure of 4 determined on the basis of spectroscopic 
data, Table 2, showed to be coincident to that of lopholide 5,10 
Figure 1. Comparison of the chemical shifts of compound 4 with 
those of lopholide showed strong differences at H-7, Me-19 and 
also at C-7, C-8, and C-9, indicative of changes in the stereo- 
chemistry of the 7,8-epoxide ring, Table S2 (Supplementary 
data). The NOE correlation between H3-I9 and H-7, Figure 2, 
evidences a cis-epoxide with an opposite configuration at C-8 to 
that corresponding to lopholide. On the other hand, comparison 
of the coupling constants of H2-9, H-10, H-ll, H-13, and H2-14 
with those of synthetic 8-epi-lophotoxin 4a,5 obtained by epi- 
merization of lophotoxin 6, Figure 1, revealed that compounds 4 
and 4a possess the same relative configuration, as depicted in 
Figure 1. 
Compounds 1, 3, and 4 were isolated from a unique extract of 
Leptogorgia, therefore all of them should belong to the same enan- 
tiomeric series as 2. Thus, the absolute stereochemistry of these 
compounds have been assigned as follow: leptogorgolide 1, 
li?,4S,5S,8R,10S,HS,12S,13tf; acetate of leptodiol 3,1R,7S,8S,10S,11S,- 
12S.13R; 8-epi-lopholide 4,1R,7S,8S,10S,11S,12S,13R 
2.1. Biogenetic pathway 
Genus-dependent C-18 specific oxidation model for the 
tandem furanocembranolide/l,4-diketo-cembranoid provides evi- 
dence regarding the mechanism of the biogenesis of the bio- 
synthetic equivalent couples. To the best of our knowledge, all 
regular naturally occurring furanocembranolide (ll)/l,4-diketo- 
cembranoid (13) congeners belong to either class A (Me) or class D 
(COOMe). No 1,4-diketo-cembranoids of class B or class C have 
been so far described. The genus Sinularia, in addition to 
furanocembranolides of class D, also biosynthesizes a number 
of related l,4-diketo-nor-C-18-cembranoids, 14. From the bio- 
synthetic point of view, and considering that no nor-C-18-fur- 
anocembranolides (12) from any genus of octocorals have been 
reported, it appears reasonable to suppose that regular fur- 
anocembranolides (11) may be considered as precursors of their 
1,4-diketo-cembranoid congeners (13). Then, they could evolve to 
their corresponding nor-l,4-dicarbonyl species (14) by loss of the 
methyl group in a decarboxylative step from a Me-18 oxidation 
cascade (Fig. 3). The discovery of a nor-l,4-diketo-cembranoid, 
gorgiacerolide,6 from Pseudopterogorgia acerosa supports this 
hypothesis. 
However, from the genus Lophogorgia, that exclusively bio- 
synthesize furanocembranolides of class B (CHO), four 1,4-diketo- 
cembranoid of class A (Me) have been reported: lophodione, 
isolophodione, and epoxylophodione isolated from Lopho- 
gorgiaalba,n and isoepoxylophodione from Lophogorgia peruana8 
(Fig. 4). This finding opposes the aforementioned biogenetic 
hypothesis since the oxidation degree at C-18 has not been 
conserved, and leads to question if 1,4-diketocembranoids are, in 
these two cases, precursors of their furanocembranoid congeners. 
However, it should be noted that the species Lophogorgia chi- 
lensis, Lophogorgia cuspidata, Lophogorgia rigida, and Lophogorgia 
6032 A.R. Diaz-Marrero et al. / Tetrahedron 65 (2009) 6023-6033 
11 
furanocembranolides 
[O] 
lossC-18 
-^  
COOMe COOMe 
Class A: R = Me       | 
Class D: R = C02Mel 
Class B: R = CHO 
[O] 
rearrang. 
R 
4^A 
13 
1,4-diketo-cembranoids 
Class A: R = Me        1 
Class D: R = C02Mel 
Class B: R = CHO (unknown) 
Class C: R = COOH (unknown) 
12 
nor-C-18- 
furanocembranolides 
(unknown) 
H 
;&(/& 
14 
1,4-diketo- 
nor-C-18-cembranoids 
OEt 
gorgiacerolide o 
9 leptogorgolide 1 
Figure 5. Possible biogenesis of leptogorgolide 1. 
Figure 3. Furanocembranolides as biogenetic precursors of 1,4-diketo- and nor-C-18- 
cembranoids. 
epoxylophodione isoepoxylophodione 
Figure 4. 1,4-Diketo-cembranoids of class A (Me) isolated from L. a/ha11 and L 
peruana.8 
violacea biosynthesize furanocembranolides of class B, as expec- 
ted, but neither of them has been reported to biosynthesize 1,4- 
diketo-cembranoids of class A-D. 
Therefore, since the concept of genus-specific oxidation of C- 
18 is applicable to the tandem furanocembranolide/l,4-diketo- 
cembranoid, with the aforementioned exception, we propose 
a biogenetic route (Fig. 5) by which 1,4-diketo-cembranoids, for 
example, 1, may be originated from an oxidative cleavage of the 
furan ringlb of a furanocembranolide like 7. Insertion of 
biologically excited singlet oxygen O2 (:Ag) in the 1,4-diene of 7 
leading to 8 in an overall 1,4-addition, followed by an endoper- 
oxide cleavage to 9, could be an interesting pathway to 1, since it 
may represent an evolutionary advantage in quenching damaging 
reactive oxygen species (ROS), thus enhancing the fitness of 
Leptogorgia sp. 
Since the taxonomic work is difficult and time consuming, the 
rationalization genus/classes A-D correlation of the present study 
seems a relevant tool to facilitate taxonomic work dealing with 
several genus of octocorals. 
3. Experimental 
3.1. General procedures 
Optical rotations were measured on a Perkin-Elmer model 
343 Plus polarimeter using a Na lamp at 25 ?C. IR spectra were 
obtained with a Perkin-Elmer 1650/FT1R spectrometer. 1H NMR 
and 13C NMR, HSQC, HMBC, and COSY spectra were measured 
employing a Bruker AMX 500 instrument operating at 500 MHz 
for JH NMR and at 125 MHz for 13C NMR. Two-dimensional NMR 
spectra were obtained with the standard Bruker software. EIMS 
and HRMS data were taken on a Micromass Autospec spec- 
trometer. HPLC separations were performed with a Hewlett- 
Packard 1050 (Jaigel-Sil semipreparative column, 10 |im, 
20x250 mm) with hexane/EtOAc mixtures. The gel filtration 
column (Sephadex LH-20) used hexane/MeOH/CH2Cl2 (3:1:1) as 
eluent. The spray reagent for TLC was H2S04/H20/AcOH (1:4:20). 
3.2. Biological material 
Leptogorgia sp. was collected by SCUBA diving off Jicarita 
(Panama) at -15 m. A voucher specimen has been deposited at 
Smithsonian Tropical Research Institute (Panama) with code 
200511. 
3.3. Extraction and isolation 
Specimens of Leptogorgia sp. were extracted with acetone at 
room temperature and were concentrated to give a dark residue 
(44.2 g). The extract was partitioned between EtOAc (3x100 mL) 
and water (100 mL). The EtOAc extracts were combined to obtain 
a brown oil (24.5 g). Vacuum flash chromatography of the organic 
extract gave three fractions (30-50% hexane/EtOAc) containing 
cembranolides, as indicated by their ^H NMR spectra. The fractions 
were further chromatographed by molecular exclusion LH-20 and 
HPLC to give compounds 1 (9.8 mg), 2 (34.8 mg), 3 (12.6 mg) and 4 
(13.8 mg), and the known compounds pukalide (32.5 mg) and E- 
deoxypukalide (4.3 mg). 
3,3. L Compound 1 
Colorless oil, [a]D? -61 (c 0.23, CH2C12); :H (CDC13, 500 MHz) 
and 13C NMR (CDCI3, 125 MHz) data, see Table 1; EIMS mjz 404 
(100) [M-AcOH]+, 372 (67) [M-AcOH-MeOH]+, 346 (32); HREIMS 
A.R. Diaz-Marrero et al. / Tetrahedron 65 (2003) 6029-6033 6033 
mjz 404.1457 (calcd for C21H24O8, 404.1471); IR (film) vmax 1785, 
1765,1740,1234, cm"1. 
3.3.2. Compound 2 
Colorless oil, [<%]jf +44 (c 0.41, CH2C12); XH (CDC13,500 MHz) and 
13C NMR (CDCI3, 125 MHz) data, see Table 1; EIMS mjz 464 (0.2) 
[M]+, 446 (0.6) [M-H20]+, 355 (1), 237 (13), 168 (100); HRE1MS mjz 
464.1666 (calcd for C^H^O^. 464.1682), 446.1598 (calcd for 
C23H26O9 464.1577); IR (film) ?? 3480, 2952, 1783, 1716, 1442, 
1375,1232 cm"1. 
3.3.3. Compound 3 
Colorless oil, [a]l? +27 (c 0.49, CH2C12); :H (CDC13, 500 MHz) 
and 13C NMR (CDC13,125 MHz) data, see Table 1; EIMS mjz 506 (0.6) 
[M]+, 446 (2) [M-AcOH]+, 355 (5), 168 (100); HREIMS mjz 506.1809 
(calcd for C25H3oOn, 506.1788), 446.1585 (calcd for C23H2609 
464.1577); IR (film) !>max 3483, 2952, 1783, 1731, 1440, 1373, 
1232 cm"1. 
3.3.4. Compound 4 
Colorless oil, [a]D? -22 (c 0.41, CH2C12); JH (CDCI3, 500 MHz) and 
13C NMR (CDCI3, 125 MHz) data, see Table 1; EIMS mjz 446 (75) 
[M]+, 386 (31) [M-AcOH]+, 168 (100); HREIMS mjz 446.1546 (calcd 
for C23H28O10,446.1577); IR (film) ymax 2954,1788,1738,1721,1715, 
1646,1615,1578,1228 cm -1 
3.3.5. (R)- and (S)-MPA ester derivatives 2a and 2b 
A solution of compound 2 (2.8 mg, 6.0x10 3 mmol) in 1.0 mL of 
CH2C12 was treated with N,N'-dicyclohexylcarbodiimide (2.5 mg, 
1.2x10 ^ mmol), 4-dimethylaminopyridine (5.0 mg, 4.1 xl0~2 mmol), 
and (R)-a-methoxy-a-phenylacetic acid (6.5 mg, 3.9x10 ^ mmol) and 
stirred at room temperature for 1 h. After filtration, the reaction mixture 
was purified by silica gel chromatography (hexane/EtOAc 1:1) to give 
the (R)-MPA ester derivative 2a (1.9 mg, 3.1 xlO 3 mmol, 51.7% yield). 
The same experimental procedure was followed to obtain the (S)-MPA 
ester derivative 2b (2.1 mg, 3.5x10 3 mmol, 58.3% yield). 
3.3.6. Acetylation of 2 
A solution of compound 2 (6.4 mg, 1.4x10 ^ mmol) in dry C5H5N 
(0.5 mL) was treated with Ac20 (0.3 mL), stirred at room temperature 
for 12 h, then poured into 5% aqueous HC1, and extracted with CH2C12. 
The reaction mixture was purified on HPLC (hexane/EtOAc 1:1) to 
give a compound (6.0 mg, 1.2x10 ^ mmol, 85.7% yield) that showed 
a H NMR spectrum coincident to that for the natural compound 3. 
Acknowledgements 
This work was supported by the Ministerio de Educacion y 
Ciencia (B1O2007-61745, SAF2006-03004), DGU1 Gobierno de 
Canarias (P1O42005, PUB2005/030), and Convenio de Cooperacion 
Universidad de Chile-CSIC, ref: 2006CL0041. A.R.D.-M. acknowl- 
edges financial support from Programa Juan de la Cierva (Ministerio 
de Educacion y Ciencia of Spain). The STRI provided facilities and J. 
del Rosario provided technical support. The Government of Panama 
granted permission for the collection of samples. 
Supplementary data 
Supplementary data associated with this article can be found in 
the online version, at doi:10.1016/j.tet.2009.05.068. 
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