Ten-membered substituted cyclic 2-oxecanone (decalactone) derivatives from Latrunculia corticata, a red sea sponge

Article abstract of DOI:10.1002/ejoc.200300012

Two novel glycosides, latrunculinosides A and B, containing substituted 2-oxecanones (decalactones) were isolated from Latrunculia corticata collected in the Gulf of Aqaba, Israel. They were characterized by spectroscopic methods, predominantly ¹H NMR, ¹³C NMR, MS, IR and UV, and by chemical degradation. Both glycosides contain unusual saccharides such as β-D-olivose, β-L-digitoxose, α-L-amicetose, and β-D-oliose. The compounds gave positive results in antifeeding activity assays. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300012

FULL PAPER
Ten-Membered Substituted Cyclic 2-Oxecanone (Decalactone) Derivatives from
Latrunculia corticata, a Red Sea Sponge
[a]
[a]
ˇ
´ˇ
Tomas Rezanka* and Valery M. Dembitsky
Keywords: Glycosides / Lactones / Natural products / Marine sponges
Two novel glycosides, latrunculinosides A and B, containing
substituted 2-oxecanones (decalactones) were isolated from
such as β-
D-olivose, β-L-digitoxose, α-L-amicetose, and β-D-
oliose. The compounds gave positive results in antifeeding
Latrunculia corticata collected in the Gulf of Aqaba, Israel. activity assays.
They were characterized by spectroscopic methods, predom-
inantly 1H NMR, 13C NMR, MS, IR and UV, and by chemical
degradation. Both glycosides contain unusual saccharides
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
tracts from Latrunculia corticata collected in the Gulf of
Aqaba, Israel, exhibited considerable biological activity.
The sponges were extracted with butanol and the extract
was separated on Sephadex LH-20. The fractions were
further purified by RP-HPLC to give two glycosides (1 and
10 Ϫ see Figure 1), which were identified by their IR, UV,
MS, and 1H and 13C NMR spectroscopic data and by
chemical degradation.
Compound 1 (latrunculinoside A) had the molecular for-
mula C40H59ClO12, established by HRFABMS (m/z ϭ
767.3776 [M ϩ H]ϩ ∆ 3.0 mmu). Negative FABMS gave
four prominent ions at m/z ϭ 765 [M Ϫ H]Ϫ, m/z ϭ 651
[M Ϫ H Ϫ 114]Ϫ, m/z ϭ 521 [M Ϫ H Ϫ 114 Ϫ 130]Ϫ, and
m/z ϭ 391 [M Ϫ H Ϫ 114 Ϫ 2 ϫ 130]Ϫ, the last three
corresponding to the loss of one trideoxyhexosyl and two
dideoxyhexosyl units, respectively. Infrared absorptions at
3550 and 1725 cmϪ1 revealed the presence of hydroxy and
carbonyl functionalities, respectively. The UV spectrum
indicated the presence of a conjugated tetrane (λmax ϭ 307
nm, log ε ϭ 4.82),[14] as was also supported by the NMR
spectroscopic data. Fortunately, the 1H NMR spectra meas-
ured in a CD3OD/[D6]DMSO mixture displayed well sepa-
rated signals, which enabled us to determine the gross struc-
ture of 1. Interpretation of the COSY and HMBC, together
with the HOHAHA and HMQC spectra, is described be-
low.
Marine sponges belonging to the class Demospongiae
have been the subject of extensive chemical and biological
investigations. Numerous bioactive peptides have been iso-
lated and identified in sponges,[1] and the continued interest
of chemists in these marine organisms has yielded a large
number of non-nitrogen-containing metabolites.[2] Sponges
have also proven to be a rich source of a broad spectrum
of natural products containing macrolactones, with fasci-
nating structures and different biological activities.[3Ϫ5] The
first compounds in this group were halicholactone and neo-
halicholactone, fatty acid metabolites found in the sponge
Halichondria okadai, collected off the coast of Japan.[6,7]
Similar compounds, didemnilactones A and B or neodi-
demnilactone,[8,9] were isolated from the colonial Didemnum
moseleyi near the Japanese Islands and asciditrienolide A[10]
from a marine tunicate (ascidian) Didemnum candidum. The
correct structure of asciditrienolide was reported a few ye-
ars later.[11]
Here we report the isolation of the ten-membered ring
lactonic glycosides latrunculinosides A and B from the
sponge Latrunculia corticata. These compounds were as-
signed the structures 1 and 10 on the basis of chemical and
spectroscopic methods.
Results and Discussion
The glycoside was enzymatically hydrolyzed (Figure 2),
and the aglycon latrunculin A (2) was isolated from the re-
action mixture. The molecular formula of 2 was determined
by HRFABMS as C22H29ClO4 ([M ϩ H]ϩ at m/z ϭ
393.1830). The LREIMS of 2 showed molecular ions at
m/z ϭ 392 and 394 in a ratio of about 3:1, indicating the
presence of one chlorine atom in 2. The side chain showed
a UV spectrum suggesting the presence of a conjugated
tetraene system (as α-parinaric acid; λmax ϭ 313, log ε ϭ
4.94), as was also implied by the proton and carbon signals
In the course of our program devoted to the search for
new compounds in marine animals[12,13] we found that ex-
[a]
Institute of Microbiology,
´
ˇ
´
Vıdenska 1083, Prague, 14220, Czech Republic
Fax: (internat.) ϩ420-241-062347
E-mail: rezanka@biomed.cas.cz
[b]
Department of Pharmaceutical Chemistry and Natural
Products, School of Pharmacy, Hebrew University of
Jerusalem,
P.O. Box 12065, Jerusalem 91190, Israel
2144
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300012
Eur. J. Org. Chem. 2003, 2144Ϫ2152

Ten-Membered Substituted Cyclic 2-Oxecanone (Decalactone) Derivatives
FULL PAPER
Figure 1. Structure of new glucosides (latrunculinosides A and B; 1 and 10) from Latrunculia corticata, a Red Sea sponge
Figure 2. Reaction schemes for degradation compounds from glycoside 1 (10) and synthesis of standard 2,3-O-isopropylidene--ribitol (4)
Eur. J. Org. Chem. 2003, 2144Ϫ2152
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2145

ˇ
T. Rezanka, V. M. Dembitsky
FULL PAPER
(see Table 1, Table 2 and Table 3). The 13C NMR spectrum gated tetraene, while two isolated (E,Z) double bonds were
contained the expected 22 signals with 27 attached protons, shown to be present in the molecule of aglycon 2.
which required that there be two hydroxy groups in com-
The presence of two hydroxy groups attached at C-7 and
pound 2. The 13C NMR spectrum contained signals due to C-8 in 2 followed from the formation of the acetonide 3,
a lactone carbonyl at δ ϭ 172.3 ppm and six olefinic bonds. with the characteristic downfield shifts experienced by the
Since the molecular formula requires eight unsaturation signals assigned to 7-H and 8-H (∆δ ϭ 0.60 and
equivalents, compound 2 must be monocyclic.
0.67 ppm, respectively).
Chemical shifts indicated that four methine carbons (C-
Further analysis of the COSY spectrum allowed us to
1
4, C-7, C-8, and C-9) resonating between δ ϭ 65.9 and δ ϭ trace the H-1H couplings of a moiety from 2-H2 to the 22-
79.3 ppm are attached to heteroatoms and the quaternary H3 methyl group, and these assignments were confirmed by
carbon C-1 belongs to an ester-type carbonyl group. Analy- the HMQC and HMBC data .
1
sis of the corresponding H NMR spectrum revealed that
The relative stereochemistry was inferred from the large
the remaining methine protons resonating between δ ϭ 5.36 couplings between α 9-H and 10-H (14.0 Hz), and between
ppm and δ ϭ 6.91 ppm are part of the (Z,E,E,Z) conju- α 5-H and β 4-H (14.0 Hz) and 6-H (15.3 Hz). These coup-
1
Table 1. H NMR data for latrunculinosides A and B (1 and 10)
No.
1
10
2α
2β
3α
3β
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
2.25 (ddd, J ϭ 11.9, 3.5, 3.1 Hz, 1 H)
2.07 (ddd, J ϭ 11.9, 14.8, 4.8 Hz, 1 H)
2.20 (dddd, J ϭ 10.8, 4.8, 3.5, 2.5, 1 H)
1.96 (dddd, J ϭ 14.8, 13.5, 10.8, 3.1, 1 H)
3.95 (dddd, J ϭ 14.5, 13.5, 2.5, 1.1, 1 H)
5.73 (dd, J ϭ 14.5, 15.8 Hz, 1 H)
5.82 (ddd, J ϭ 15.8, 4.4, 1.1 Hz, 1 H)
4.07 (dd, J ϭ 4.4, 3.2 Hz, 1 H)
4.38 (dd, J ϭ 3.2, 14.6 Hz, 1 H)
5.58 (dd, J ϭ 14.6, 14.1 Hz, 1 H)
5.44 (dd, J ϭ 14.1, 12.3 Hz, 1 H)
6.37 (dd, J ϭ 12.3, 11.5 Hz, 1 H)
6.93 (dd, J ϭ 11.5, 14.7 Hz, 1 H)
6.38 (dd, J ϭ 14.7, 11.2 Hz, 1 H)
6.49 (dd, J ϭ 11.2, 13.8 Hz, 1 H)
6.51 (dd, J ϭ 13.8, 11.3 Hz, 1 H)
6.16 (dd, J ϭ 11.3, 10.8 Hz, 1 H)
5.66 (ddd, J ϭ 10.8, 6.4, 6.4 Hz, 1 H)
2.63 (t, J ϭ 6.4 Hz, 2 H)
2.27 (m, 1 H)
2.09 (m, 1 H)
2.08 (m, 2 H)
4.15 (ddd, J ϭ 14.6, 13.1, 2.4 Hz, 1 H)
5.93 (dd, J ϭ 14.5, 10.6 Hz, 1 H)
5.87 (dd, J ϭ 10.6, 4.5 Hz, 1 H)
4.27 (dd, J ϭ 4.5, 3.1 Hz, 1 H)
3.88 (dd, J ϭ 3.1, 14.6 Hz, 1 H)
5.08 (dd, J ϭ 14.6, 14.2 Hz, 1 H)
5.46 (dd, J ϭ 14.2, 12.2 Hz, 1 H)
6.06 (dd, J ϭ 12.2, 11.6 Hz, 1 H)
6.44 (dd, J ϭ 11.6, 14.8 Hz, 1 H)
6.40 (dd, J ϭ 14.8, 11.4 Hz, 1 H)
6.51 (dd, J ϭ 11.4, 13.9 Hz, 1 H)
6.57 (dd, J ϭ 13.9, 11.6 Hz, 1 H)
6.10 (dd, J ϭ 11.6, 10.4 Hz, 1 H)
5.68 (ddd, J ϭ 10.4, 6.3, 6.3 Hz, 1 H)
2.64 (t, J ϭ 6.3 Hz, 2 H)
5.45 (m, 1 H)
19
5.43 (m, 1 H)
20
21
5.37 (m, 1 H)
2.00 (m, 2 H)
5.39 (1H. m)
2.01 (m, 2 H)
22
1Ј
2aЈ
2eЈ
3Ј
4Ј
5Ј
6Ј
1ЈЈ
2aЈЈ
2eЈЈ
3ЈЈ
4ЈЈ
5ЈЈ
6ЈЈ
1ЈЈЈ
2aЈЈЈ
2eЈЈЈ
3aЈЈЈ
3eЈЈЈ
4ЈЈЈ
5ЈЈЈ
6ЈЈЈ
1.06 (t, J ϭ 7.6 Hz, 3 H)
1.04 (t, J ϭ 7.6 Hz, 3 H)
4.85 (dd, J ϭ 10.0, 1.5 Hz, 1 H)
2.40 (ddd, 1 H, J ϭ 12.5, 10.5, 10.0)
2.24 (ddd, J ϭ 10.5, 4.1, 1.5 Hz, 1 H)
3.23 (ddd, J ϭ 12.5, 4.6, 4.1 Hz, 1 H)
3.34 (dd, J ϭ 4.8, 4.6 Hz, 1 H)
3.85 (dd, J ϭ 6.4, 4.8 Hz, 1 H)
1.29 (d, J ϭ 6.4 Hz, 3 H)
5.05 (dd, J ϭ 10.5, 2.1 Hz, 1 H)
2.65 (ddd, J ϭ 10.8, 10.5, 9.2 Hz, 1 H)
2.15 (ddd, J ϭ 10.8, 5.2, 2.1 Hz, 1 H)
3.14 (ddd, J ϭ 9.2, 5.2, 5.0 Hz, 1 H)
3.08 (dd, J ϭ 5.0, 4.5 Hz, 1 H)
3.74 (dd, J ϭ 4.5, 6.4 Hz, 1 H)
1.39 (d, J ϭ 6.4 Hz, 3 H)
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
4.93 (dd, J ϭ 1.7, 9.8 Hz, 1 H)
1.67 (ddd, J ϭ 10.7, 9.8, 3.3 Hz, 1 H)
2.01 (ddd, J ϭ 10.7, 2.8, 1.7 Hz, 1 H)
3.28 (dt, J ϭ 3.3, 2.8 Hz, 1 H)
3.55 (dd, J ϭ 9.4, 2.8 Hz, 1 H)
3.94 (dq, J ϭ 9.4, 6.4 Hz, 1 H)
1.31 (d, J ϭ 6.4 Hz, 3 H)
4.74 (dd, J ϭ 11.0, 1.3 Hz, 1 H)
1.55 (ddd, 1 H, J ϭ 11.8, 11.0, 10.3)
2.19 (ddd, J ϭ 10.3, 4.7, 1.3 Hz, 1 H)
3.68 (ddd, J ϭ 11.8, 8.2, 4.7 Hz, 1 H)
3.28 (dd, J ϭ 9.7, 8.2 Hz, 1 H)
3.56 (dd, J ϭ 9.7, 6.4 Hz, 1 H)
1.32 (d, J ϭ 6.4 Hz, 3 H)
5.02 (d, J ϭ 2.4 Hz, 1 H)
2.03 (m, 1 H)
1.75 (m, 1 H)
1.92 (m, 1 H)
1.73 (m, 1 H)
3.08 (ddd, J ϭ 9.9, 9.5, 4.3 Hz, 1 H)
3.31 (dq, J ϭ 9.9, 6.4 Hz, 1 H)
1.19 (d, J ϭ 6.4 Hz, 3 H)
2146
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 2144Ϫ2152

Ten-Membered Substituted Cyclic 2-Oxecanone (Decalactone) Derivatives
FULL PAPER
1
Table 2. H NMR data for latrunculins A and B (2 and 11) and their derivatives (3 and 12)
No.
2α
2
3
11
12
2.25 (ddd, J ϭ 11.7,
3.2, 3.0 Hz, 1 H)
2.07 (ddd, J ϭ 11.7,
14.4, 4.7 Hz, 1 H)
2.20 (dddd, J ϭ 10.8,
4.7, 3.2, 2.6, 1 H)
1.96 (dddd, J ϭ 14.4,
13.4, 10.8, 3.0,1 H)
4.05 (ddd, J ϭ 14.0,
13.4, 2.6 Hz, 1 H)
5.77 (dd, J ϭ 14.0,
15.3 Hz, 1 H)
2.24 (ddd, J ϭ 11.9,
3.5, 3.1 Hz, 1 H)
2.08 (ddd, J ϭ 11.9,
14.8, 4.8 Hz, 1 H)
2.21 (dddd, , J ϭ 10.8,
4.8, 3.5, 2.5 1 H)
1.95 (dddd, J ϭ 14.8,
13.5, 10.8, 3.1, 1 H)
3.95 (ddd, J ϭ 14.5,
13.5, 2.5 Hz, 1 H)
5.73 (dd, J ϭ 14.5,
15.8 Hz, 1 H)
2.27 (ddd, J ϭ 11.6,
3.5, 3.2 Hz, 1 H)
2.09 (ddd, J ϭ 11.6,
14.3, 4.9 Hz, 1 H)
2.19 (dddd, 1 H, , J ϭ 10.8,
4.9, 3.5, 2.4)
1.97 (dddd, 1 H, J ϭ 14.3,
13.3, 10.8, 3.2)
4.15 (ddd, J ϭ 14.5,
13.3, 2.4 Hz, 1 H)
5.91 (dd, J ϭ 14.5,
10.5 Hz, 1 H)
2.26 (ddd, J ϭ 11.5,
3.4, 3.1 Hz, 1 H)
2.06 (ddd, J ϭ 11.5,
14.7, 4.8 Hz, 1 H)
2.22 (dddd, J ϭ 10.8,
4.8, 3.4, 2.5, 1 H)
1.98 (dddd, J ϭ 14.7,
13.5, 10.8, 3.1, 1 H)
3.95 (ddd, J ϭ 14.4,
13.5, 2.5 Hz, 1 H)
5.73 (dd, J ϭ 14.4,
10.8 Hz, 1 H)
2β
3β
4
5
6
5.89 (dd, J ϭ 15.3,
4.7 Hz, 1 H)
5.82 (dd, J ϭ 15.8,
4.3 Hz, 1 H)
5.81 (dd, J ϭ 10.5,
4.5 Hz, 1 H)
5.82 (dd, J ϭ 10.8,
4.4 Hz, 1 H)
7
3.97 (dd, J ϭ 4.7,
3.3 Hz, 1 H)
4.57 (dd, J ϭ 4.3,
3.1 Hz, 1 H)
3.98 (dd, J ϭ 4.5,
3.3 Hz, 1 H)
4.59 (dd, J ϭ 4.4,
3.1 Hz, 1 H)
8
3.94 (dd, J ϭ 3.3,
14.8 Hz, 1 H)
4.61 (dd, J ϭ 3.1,
14.5 Hz, 1 H)
3.96 (dd, J ϭ 3.3,
14.6 Hz, 1 H)
4.55 (dd, J ϭ 3.1,
14.7 Hz, 1 H)
9
4.88 (dd, J ϭ 14.8,
14.0 Hz, 1 H)
4.98 (dd, J ϭ 14.5,
14.1 Hz, 1 H)
4.72 (dd, J ϭ 14.6,
14.0 Hz, 1 H)
4.96 (dd, J ϭ 14.7,
14.3 Hz, 1 H)
10
11
12
13
14
15
16
17
18
5.54 (dd, J ϭ 14.0,
12.4 Hz, 1 H)
6.35 (dd, J ϭ 12.4,
11.7 Hz, 1 H)
6.91 (dd, J ϭ 11.7,
14.6 Hz, 1 H)
6.39 (dd, J ϭ 14.6,
11.1 Hz, 1 H)
6.46 (dd, J ϭ 11.1,
13.6 Hz, 1 H)
6.51 (dd, J ϭ 13.6,
11.5 Hz, 1 H)
6.14 (dd, J ϭ 11.5,
10.6 Hz, 1 H)
5.68 (ddd, J ϭ 10.6,
6.3, 6.3 Hz, 1 H)
2.64 (t, J ϭ 6.3 Hz,
2 H)
5.51 (dd, J ϭ 14.1,
12.5 Hz, 1 H)
6.38 (dd, J ϭ 12.5,
11.6 Hz, 1 H)
6.93 (dd, J ϭ 11.6,
14.7 Hz, 1 H)
6.40 (dd, J ϭ 14.7,
11.2 Hz, 1 H)
6.48 (dd, J ϭ 11.2,
13.8 Hz, 1 H)
6.50 (dd, J ϭ 13.8,
11.3 Hz, 1 H)
6.17 (dd, J ϭ 11.3,
10.7 Hz, 1 H)
5.66 (ddd, J ϭ 10.7,
6.2, 6.2 Hz, 1 H)
2.66 (t, J ϭ 6.2 Hz,
2 H)
5.54 (dd, J ϭ 14.0,
12.6 Hz, 1 H)
6.36 (dd, J ϭ 12.6,
11.5 Hz, 1 H)
6.92 (dd, J ϭ 11.5,
14.8 Hz, 1 H)
6.36 (dd, J ϭ 14.8,
11.0 Hz, 1 H)
6.49 (dd, J ϭ 11.0,
13.7 Hz, 1 H)
6.52 (dd, J ϭ 13.7,
11.4 Hz, 1 H)
6.15 (dd, J ϭ 11.4,
10.8 Hz, 1 H)
5.69 (ddd, J ϭ 10.8,
6.4, 6.4 Hz, 1 H)
2.63 (t, J ϭ 6.4 Hz,
2 H)
5.51 (dd, J ϭ 14.3,
12.4 Hz, 1 H)
6.37 (dd, J ϭ 12.4,
11.2 Hz, 1 H)
6.90 (dd, J ϭ 11.2,
14.6 Hz, 1 H)
6.41 (dd, J ϭ 14.6,
11.5 Hz, 1 H)
6.50 (dd, J ϭ 11.5,
13.7 Hz, 1 H)
6.53 (dd, J ϭ 13.7,
11.0 Hz, 1 H)
6.18 (dd, J ϭ 11.0,
10.6 Hz, 1 H)
5.64 (ddd, J ϭ 10.6,
6.5, 6.5 Hz, 1 H)
2.65 (t, J ϭ 6.5 Hz,
2 H)
19
20
5.45 (m, 1 H)
5.36 (m, 1 H)
5.43 (m, 1 H)
5.38 (m, 1 H)
5.47 (m, 1 H)
5.37 (m, 1 H)
5.44 (m, 1 H)
5.39 (1H. m)
21
22
CH3
CH3
2.00 (m, 2 H)
1.03 (t, J ϭ 7.4 Hz, 3 H)
Ϫ
2.01 (m, 2 H)
1.05 (t, J ϭ 7.5 Hz, 3 H)
1.40 (s, 1 H)
2.03 (m, 2 H)
1.06 (t, J ϭ 7.3 Hz, 3 H)
Ϫ
2.05 (m, 2 H)
1.04 (t, J ϭ 7.4 Hz, 3 H)
1.41 (s, 1 H)
Ϫ
1.40 (s, 1 H)
Ϫ
1.41 (s, 1 H)
lings point to the anti orientations shown in Figure 3, while tation (ribo). These findings suggest that 2, as depicted in
the small couplings exhibited by 6-H and 7-H (4.7 Hz), and Figure 4, has the (4R*,7R*,8R*,9S*; i.e., relative) configu-
also by 7-H and 8-H (3.3 Hz), are compatible with syn in- ration.
teractions. In the NOE difference spectrum of 2, the 8-H
The absolute stereochemistry of 2 was determined as fol-
and 4-H signals showed peak enhancements when 6-H was lows. When the isopropylidene derivative 3, which retained
irradiated. When 5-H was irradiated, the 3-H and 9-H sig- the asymmetric carbons (C-4, C-7, C-8, C-9) in 2, was sub-
nals showed peak enhancements. Furthermore, the NOEs jected successively to ozonolysis and NaBH3CN reduction,
observed for β 4-H and 8-H upon irradiation of 6-H, as it afforded the isopropylidene of ribitol (4), [α]2D1 ϭ ϩ4.0
well as the NOEs observed between 9-H, 5-H, and α 3-H (c ϭ 0.35). Our ribitol (4) was directly compared with both
and 10-H, 8-H, 6-H, 4-H, and α H-2, are in agreement with its  and  epimers, prepared in our lab by the reported
the above evidence (see Figure 3).
method,[15] and our synthesized  epimer was found to be
The results from MM2 calculations and molecular identical in all respects (1H NMR, 13C NMR, and optical
modeling, together with those described above, indicated rotation) with the  isomer[16] derived from -ribose. There-
that the most stable conformation of 2 has all three hydroxy fore, 4 has the (7R,8R,9S) absolute configuration, and so 2
groups at C-7, C-8, and C-9 located with the same orien- has the (4R,7R,8R,9S) absolute configuration, and latrun-
Eur. J. Org. Chem. 2003, 2144Ϫ2152
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2147

ˇ
T. Rezanka, V. M. Dembitsky
FULL PAPER
Table 3. 13C NMR data for latrunculinosides A and B (1 and 10),
latrunculins A and B (2 and 11), and their derivatives (3 and 12)
this monosaccharide is β-digitoxose (2,6-dideoxy-β-ribo-
hexose).
As to the second monosaccharide, strong NOEs were ob-
served between H-lЈЈ/3Ј-HЈ, H-lЈЈ/5ЈЈ-H, and 3ЈЈ-H/5ЈЈ-H,
while strong J couplings appeared between H-lЈЈ/2aЈ-HЈ,
2aЈ-HЈ/3ЈЈ-H, 3ЈЈ-H/4Ј-HЈ, and 4ЈЈ-H/5ЈЈ-H. These obser-
vations indicate that this monosaccharide is β-olivose (2,6-
dideoxy-β-arabino-hexopyranose).
The coupling constants (J ϭ 9.9 Hz) between 4ЈЈЈ-H and
5ЈЈЈ-H of the monosaccharide indicate diaxial orientations.
The anomeric proton 1Ј-HЈЈ appears as doublet (J ϭ
No.
1
2
3
10
11
12
1
2
3
4
5
6
7
8
172.0
34.7
25.4
70.3
129.4
135.9
73.6
74.8
71.9
127.0
134.8
127.5
134.6
131.2
134.2
122.5
125.7
24.4
124.5
129.9
20.2
14.0
100.4
39.1
63.8
76.5
69.7
19.1
99.5
37.6
70.6
80.7
71.3
17.7
97.1
25.2
32.0
71.4
71.2
18.5
Ϫ
172.3
33.0
28.8
65.9
129.3
133.4
75.8
79.3
71.8
128.7
132.1
129.9
134.5
131.4
134.2
122.4
125.8
24.3
124.2
129.4
20.1
14.2
Ϫ
172.1
32.9
29.4
65.6
129.2
132.3
79.4
84.7
72.0
131.0
128.1
129.7
134.3
131.5
134.4
122.2
125.9
24.0
124.6
128.5
20.3
14.1
Ϫ
172.0
33.4
26.0
69.0
129.7
134.1
72.5
73.5
72.1
128.2
133.1
127.5
134.8
131.7
133.5
123.1
126.1
26.2
124.9
130.4
20.1
14.2
98.1
32.2
62.0
77.6
68.7
14.9
97.6
34.1
64.4
79.5
68.4
14.9
Ϫ
172.2
33.0
29.1
66.8
129.0
133.2
74.2
78.7
70.9
127.9
132.4
128.7
133.1
132.6
133.8
123.0
125.3
25.1
124.8
128.7
20.0
14.2
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
172.1
32.8
29.7
67.1
129.4
131.7
77.8
82.3
9
71.5 2.4 Hz). On the basis of data from 2D NMR (i.e., COSY
10
11
12
13
14
15
16
17
18
19
20
21
22
1Ј
130.9
129.9
129.0
133.7
132.4
133.1
122.7
125.7
24.6
and NOE), the monosaccharide was identified as α-amice-
tose (2,3,6-trideoxy-α-erythro-hexopyranose).
The monosaccharides from the hydrolysate of 1 were
purified by NH2-HPLC. After evaporation of eluent, the
three saccharides were obtained as colorless syrups. The
first peak (amicetose) had [α]2D1 ϭ Ϫ39.4. Catelani[17] gave
[α]D ϭ Ϫ39.0 for an α,β-anomeric mixture of -amicetose.
1
In addition, the H NMR spectrum is in good agreement
124.7
128.5 with published data.[18] The optical rotation value of our
20.3
14.1
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
olivose was ϩ24, which is practically identical with the re-
ported[19] value for -olivose ([α]D ϭ ϩ22). The optical ro-
tation of the compound corresponding to the third peak
2Ј
3Ј
4Ј
5Ј
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
(digitoxose) in water ([α]2D1 ϭ Ϫ37) was also in good agree-
ment with the literature data[20] ([α]D ϭ Ϫ38 for the  and
[α]D ϭ 36.5 for the  configuration). This result indicates
that one monosaccharide of compound 1 is in the -form
and two in the -form.
6Ј
1ЈЈ
2ЈЈ
3ЈЈ
4ЈЈ
5ЈЈ
6ЈЈ
1ЈЈЈ
2ЈЈЈ
3ЈЈЈ
4ЈЈЈ
5ЈЈЈ
6ЈЈЈ
C
In compound 1, the glycosidation shift at C-8 (ca.
ϩ4.5 ppm) and the chemical shifts of 1Ј-H (δ ϭ 4.93 ppm)
and C-1Ј (δ ϭ 100.4 ppm) of digitoxose indicated that this
monosaccharide was glycosidated at C-8 of the aglycon.
The signal due to the anomeric proton (1ЈЈ-H) of olivose
(δ ϭ 4.74 ppm), correlating to the C-1ЈЈ resonance at δ ϭ
99.5 ppm by HETCOR, indicated that the olivose unit was
linked to a secondary alcoholic carbon (C-4Ј of the digi-
toxose). The amicetose was assigned as terminal by the ab-
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
101.8
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
101.8
28.7
28.7
CH3
CH3
Ϫ
Ϫ
Ϫ
Ϫ
28.7 sence of any glycosylation shift at 4ЈЈЈ-H and/or C-4ЈЈЈ.
28.7
These deductions were confirmed by a COLOC spectrum,
which showed some diagnostic long-range correlations be-
tween 1Ј-H of digitoxose (δ 4.93) and C-8 (δ 74.8) of the
aglycon, between 1ЈЈ-H (δ ϭ 4.74 ppm) of the olivose unit
culin
A
is
therefore
(4R,5E,7R,8R,9S,10Z,12E, and C-4Ј (δ 76.5) of digitoxose, and between 1ЈЈЈ-H (δ ϭ
14E,16Z,19Z)-4-chloro-7,8-dihydroxy-5,10,12,14,16,19-do- 5.02 ppm) of the amicetose unit and C-4ЈЈ (δ ϭ 80.7 ppm)
cosahexaeno-9-lactone.
of olivose (see Table 1). The structure of glycoside 1 was
1
The H NMR and 13C NMR spectroscopic data of the thus (8R)-8-O-α--amicetosyl-(1Ǟ4)-β--olivosyl-(1Ǟ4)-β-
saccharide unit of 1 are also shown in Table 1 and Table 3. -digitoxosyl latrunculin A (i.e., latrunculinoside A).
1H and 13C NMR spectroscopic data, as well as decoupling
High-resolution FABMS analysis of 10 suggested a mo-
experiments on 1, were used to assign the signals of the lecular formula of C34H49ClO10. The negative FABMS gave
monosaccharide moieties. For a dideoxyhexose, strong J an [M Ϫ H]Ϫ ion at m/z ϭ 650, with prominent fragments
coupling were observed between 1Ј-H/2aЈ-H and 4Ј-H/5Ј-H at m/z ϭ 520 [M Ϫ H Ϫ 130]Ϫ and 390 [M Ϫ H Ϫ 2 ϫ
and weak coupling between 1Ј-H/2Ј-He, and 2Ј-He/3Ј-H 130]Ϫ (cleavage of one and two dideoxyhexose units, respec-
and 3Ј-H/4Ј-H, while the NOE patterns were strong only tively). The molecular formula was supported by the pres-
between 2Ј-H and 4Ј-H. The coupling constant of the ence of 34 signals in the 13C NMR spectrum (3 ϫ CH3, 6
anomeric proton of sugar was J1Ј-HϪ2aЈ-H ϭ 9.8 Hz and ϫ CH2, 24 ϫ CH, and 1 ϫ quaternary carbon). The high
J
1Ј-HϪ2eЈ-H ϭ 1.7 Hz. The glycoside linkage of the sugar was level of oxygenation in the molecular formula hinted at the
thus determined to be β. These observations indicated that presence of sugars in the molecule. The glycoside 10 was
2148
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Eur. J. Org. Chem. 2003, 2144Ϫ2152

Ten-Membered Substituted Cyclic 2-Oxecanone (Decalactone) Derivatives
FULL PAPER
Figure 3. The NOE, HMBC, and H-H COSY correlations of latrunculinoside A (1)
aglycon 11. Only the 3J value corresponding to the dihedral
angle between 5-H and 6-H was shifted (3J5-HϪ6-H
ϭ
10.5 Hz). The value of the dihedral angle conformed to a Z
double bond between C-5 and C-6. The two anomeric pro-
1
tons (δ ϭ 4.85 and 5.05 ppm ) in the H NMR spectrum
and the corresponding 13C signals (δ ϭ 98.1 ppm and 97.6
ppm) in the 13C NMR spectra revealed the presence of two
sugars (Table 3). The 1H-1H connectivities of the sugars
were determined by COSY and TOCSY experiments, which
indicated that they were both 2,6-dideoxy sugars. The sug-
ars revealed large couplings (J Ն 10 Hz) between 1-H and
2a-H, and 2a-H and 3-H, and small couplings (J ഠ 4.5 Hz)
between 3-H/4-H and 5-H, indicating it to be a β-oliose.
This was further verified by NOESY correlations of the re-
spective 1,3-diaxial protons 1-H and 2a-H (Table 2). The
proton and the carbon spectral assignments of the sugar
moieties were made possible by a combination of COSY,
TOCSY, HMQC, and HMBC experiments. The linkages
between the sugars were deduced from the HMBC corre-
lation from the anomeric proton of one sugar to the carbon
of the neighboring sugar at the position of linkage and vice
versa (see Figure 3). This allowed the two sugars to be
linked as disaccharide moiety. The HMBC correlation from
1Ј-H (δ ϭ 4.85 ppm) of the first sugar to the aglycon carbon
at δ ϭ 73.5 ppm allowed the placement of the disaccharide
at C-8 of the aglycon. The stereochemistry of our oliose
was determined by comparison with authentic -oliose (ob-
tained after hydrolysis of mithramycin A) by chiral gas
chromatography (see Exp. Sect.).
Figure 4. 3D-MM2 models (with and without side chain) of com-
pound 1 are included
enzymatically hydrolyzed analogously to compound 1, and
The relative and absolute stereochemistry of aglycon 11
the spectra of the aglycon (11; i.e., latrunculin B), were was demonstrated analogously to the case of compound 2,
practically identical Ϫ with one exception Ϫ to those of and the structure was identified as (4R,5Z,7R,8R,9S,
Eur. J. Org. Chem. 2003, 2144Ϫ2152
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2149

ˇ
T. Rezanka, V. M. Dembitsky
FULL PAPER
Table 4. Bioactivities of latrunculinosides A and B (1 and 10)
Compound[a]
10 µg/mL[b]
50 µg/mL[b]
100 µg/mL[b]
Nat. conc.[c] µg/mL
1
10
4.3Ϯ0.6
6.0Ϯ1.0
1.7Ϯ0.6
3.3Ϯ0.6
0
29.2
9.0
0.7Ϯ0.6
[a] Aquarium assay results from feeding by goldfish on pellets treated with glycoside (1 and 10). All control pellets were eaten in all assays.
[b]
Three replicate assays were performed at each concentration (mean Ϯ SD is indicated in columns 2 to 4). Concentration of the pure
[c]
compound (1 or 10) in the pellet. Natural concentration of 1 and 10 in L. corticata. Sponge volume was determined by displacement
of water with frozen material according to Pawlik.[24]
tion MS were with a VG 7070E Ϫ HF spectrometer (70 eV). GC-
MS analyses of the sugar derivatives were performed with a Finni-
gan 1020 B single-state quadrupole GC-MS instrument in the EI
mode. A C18 reversed-phase column (5 µm, 7.8 ϫ 250 mm, Supelco,
USA), was employed. A linear gradient from 40% H2O and 60%
acetonitrile to pure acetonitrile over 36 min, flow rate 1.7 mL/min
with detection at 256 nm, was used to separate the two compounds
in the crude extract.
10Z,12E,14E,16Z,19Z)-4-chloro-7,8-dihydroxy-5,10,12,14,
16,19-docosahexaeno-9-lactone (i.e., latrunculin B). The
full structure of glycoside 10 was therefore (8R) 8-O-β--
oliosyl-(1Ǟ4)-β--oliosyl latrunculin B (i.e., latrunculino-
side B).
A search for related compounds identified[21,22] pinoli-
doxin and epipinolidoxin from the fungus Aschochyta pin-
odes, and the more closely related didemnilactones AϪB,
neodidemnilactone, and ascitrienolides AϪC from the mar-
ine ascidian Didemnum. These compounds exhibit weak
binding activity to leukotriene B4 receptors in human poly-
morphonuclear leukocyte membrane fractions. They share
the same fatty acid structure element in their lactone ring
and a similar unsaturated side chain with the latrunculinos-
ides A and B.
Animal Materials: The sponge Latrunculia corticata (Carter 1879),
family Styelidae, phylum Porifera, class Demospongiae, subclass
Monaxonida, family Latrunculiidae, was collected by hand (scuba)
from the Coral Reef (from 5 to 10 m deep), on 27 August 2001 in
the Red Sea, Gulf of Aqaba (Eilat, Israel). The voucher specimens
are deposited in the collection of the second author (V.M.
Dembitsky). Latrunculia corticata, also known as Magnificant Fire
Sponge, had a brown-red color.
Neither glycoside displayed antibacterial or antifungal
activity. The compounds also did not give positive results
in a brine shrimp toxicity assay, a sea urchin eggs test (Para-
centrotus lividus), or a crown gall tumors on potato disks
test (Agrobacterium tumefaciens).
Sponges are common inhabitants of the benthos and ex-
cellent candidates for chemical defenses, inasmuch as they
have a sessile lifestyle and soft unprotected body tissues.
Some macrolactones are known to be the principal defens-
ive strategy of Caribbean sponges against predatory reef
fishes.[23] To investigate the antifeeding activity of our two
metabolites, aquarium assays were performed by previously
described methods.[24]
As shown in Table 4, both compounds (1 and 10) deter
feeding by goldfish in aquarium bioassays at concentrations
of 10Ϫ100 µg/mL, equal to their natural concentrations;
this strong bioactivity suggests a role in the chemical de-
fense of L. corticata. The trans compound (1) had a higher
activity than its cis counterpart (10). As shown in the litera-
ture[25] and confirmed by our results, halogenation increases
the antifeeding activity.
Extraction and Isolation: Fresh sponges (850 g wet weight) were
frozen and stored at Ϫ18 °C. Sample of sponge were extracted with
90% butanol. Chromatography of the extract on a Sephadex LH-
20 column (100 ϫ 5 cm) with elution with MeOH gave organic
fractions (8 mL) checked by two-dimensional TLC (silica gel plates,
nBuOH/AcOH/H2O, 12:3:5 and CHCl3/MeOH/H2O, 40:9:1). Frac-
tion 7 was further fractionated by RP-HPLC on a C18-Bondapak
column (30 cm ϫ 7.8 mm, flow rate 2.0 mL/min) with MeOH/H2O
(4:1) to yield two compounds: 1 (24.8 mg, 0.0029%) and 10
(7.7 mg, 0.0009%).
Enzymatic Hydrolysis of Glycosides (Autolysis): An aliquot of crude
extract (after extraction of BuOH) was added to 50 g of defrost
sponge and the solution was then incubated at 37 °C for 48 h. The
resulting mixture was extracted with CH2Cl2, the solution was eva-
porated to dryness, and the residue was chromatographed on a sil-
ica gel column (10 g) with CH2Cl2/MeOH/H2O (90:10:1), to afford
2 or 11.
Preparation of Isopropylidene Aglycon: The aglycon 2 (3.6 mg) was
dissolved in dry acetone (200 µL) and 2,2-dimethoxypropane
(2 mL). A catalytic amount of p-toluenesulfonic acid was added to
this solution. The reaction mixture was stirred at room temperature
for 4 h under nitrogen. After that, the mixture was neutralized with
saturated NaHCO3 solution and extracted with 3 ϫ 3 mL of
CHCl3. The combined organic layers were concentrated to dryness
in vacuo to afford the corresponding isopropylidene derivative 3
(2.9 mg).
Experimental Section
General Experimental Procedures: UV spectra were measured with
a Cary 118 (Varian) apparatus in EtOH in the 200Ϫ350 nm range.
A PerkinϪElmer Model 1310 (PerkinϪElmer, Norwalk, CT, USA)
IR spectrophotometer was used for scanning IR spectroscopy of
Ozonolysis: The isopropylidene derivative 3 was dissolved in meth-
anol (10 mL), cooled in a dry ice/acetone bath (Ϫ78 °C). Ozone
was bubbled through the solution for 5Ϫ10 min. Excess ozone was
then removed with a stream of nitrogen for 2 min. Sodium cyano-
compounds as neat films. NMR spectra were recorded with a borohydride (4 mg) was added at Ϫ78 °C and the mixture was
Bruker AMX 500 spectrometer (Bruker Analytik, Karlsruhe, Ger-
stirred for 1 h, after which acetic acid (20 µL) was added. After
stirring had continued for an additional 30 min at room tempera-
many) at 500.1 MHz (1H), 125.7 MHz (13C). High- and low-resolu-
2150
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 2144Ϫ2152

Ten-Membered Substituted Cyclic 2-Oxecanone (Decalactone) Derivatives
FULL PAPER
ture, the solution was evaporated to dryness. The residue was dis-
solved in methanol and was then chromatographed on a silica gel
column with methanol (flow rate 1 ml/ minute) to yield the main
product 4. The compound 4 was dissolved in the methanol and
10% BSTFA (N,O-bis(trimethylsilyl)trifluoroacetamide) in hexane
were added. After 3 min, 2 µL of the reaction solution was analyzed
by chiral GC (conditions see above).
Latrunculin
A
(2): (4R,5E,7R,8R,9S,10Z,12E,14E,16Z,19Z)-4-
Chloro-7,8-dihydroxy-5,10,12,14,16,19-docosahexaeno-9-lactone,
colorless oil. [α]D23 ϭ ϩ36 (c ϭ 0.09, MeOH). UV (EtOH): λmax
(log ε) ϭ 313 (4.94) nm. IR (film): ν˜max ϭ 3550 (OH), 1725 (Cϭ
O) cmϪ1. HRFABMS: m/z ϭ 393.1830 [M ϩ H]ϩ, calcd. for
[C22H29ClO4 ϩ H]ϩ 393.1832; negative LREIMS: m/z ϭ 394 [M]Ϫ,
392 [M]Ϫ in a ratio 3:1; NMR spectra see Table 1Ϫ3.
Hydrolysis of Glycosides: The glycoside (ഠ 15 mg) was dissolved in
Latrunculinoside B (10): Colorless powder (7.7 mg). [α]2D2 ϭ Ϫ18.5
hydrogen chloride (5%, 8 mL) and the mixture was heated at reflux (c ϭ 0.09, MeOH). HRFABMS: m/z ϭ 652.3100 [M ϩ H]ϩ, calcd.
for 4 h. The reaction mixture was neutralized with silver carbonate
and then filtered, and the filtrate was extracted with diethyl ether.
The water layer was evaporated to dryness and the mixture was
chromatographed on an NH2-HPLC column with water/aceto-
nitrile (8:2) to yield α,β-anomeric mixtures of -digitoxose (7)
for [C34H49ClO10 ϩ H]ϩ 653.3092; negative LRFABMS: m/z ϭ 650
[M Ϫ H]Ϫ, 520 [M Ϫ H Ϫ 130]Ϫ, 390 [M Ϫ H Ϫ 2 ϫ 130]Ϫ. The
1
UV, IR and H and 13C NMR spectra were practically identical to
those of 1, see also Table 1Ϫ3 for NMR spectroscopy.
[α]2D1 ϭ Ϫ37, -olivose (8) [α]2D1 ϭ ϩ24, and -amicetose (9) [α]2D1
Ϫ39.4, obtained as colorless syrups.
ϭ
Latrunculin
B (11): (4R,5Z,7R,8R,9S,10Z,12E,14E,16Z,19Z)-4-
Chloro-7,8-dihydroxy-5,10,12,14,16,19-docosahexaeno-9-lactone,
colorless oil. [α]2D3 ϭ Ϫ9 (c ϭ 0.08, MeOH). UV (EtOH): λmax (log
˜
ϭ 3550 (OH), 1722 (Cϭ
Chiral Chromatography: A MachereyϪNagel GmbH & Co. KG ε) ϭ 312 (4.73) nm. IR (film): νmax
(Düren, Germany) Permabond -Chirasil-Val capillary column Ϫ
25 m ϫ 0.25 mm ID Ϫ was used. Oven temperature: 80 °C (5 min
iso; 4 °C/min to) 190 °C (10 min), carrier gas helium, 20 cm/s, de-
tector FID, 300 °C, injection of 1 µL mixture in dichloromethane
(for standards: containing 0.5 mg/ml of each analyte), split (100:1),
250 °C.
O) cmϪ1. HRFABMS: m/z ϭ 393.1828 [M ϩ H]ϩ, calcd. for
[C22H29ClO4 ϩ H]ϩ 393.1832; negative LREIMS: m/z ϭ 394 [M]Ϫ
and m/z ϭ 392 [M]Ϫ in a ratio 3:1; NMR spectra see Table 1Ϫ3.
Bioassay for Antifeeding Activity Assay: Purified compounds (1 and
10) were dissolved in a minimal volume of methanol and mixed
with alginate-based food matrix[24] (100 µL) until all organic and
water-soluble components were distributed uniformly throughout
the paste. The alginate food matrix was then dispensed by use of a
0.1 mL syringe into a CaCl2 solution (0.25 ⁾, forming a strand
that was allowed to harden for 2 min. The hardened strand was
rinsed with filtered water and cut into 3 mm pellets with a scalpel.
Control pellets were prepared identically but without the addition
of natural or synthetic compounds. Feeding assays were performed
with goldfish (Carassius auratus).
Preparation of Standards
2,3-O-Isopropylidene-α/β-L-ribofuranose (6): A solution of H2SO4
in dry acetone (0.1%) was added to -ribofuranose (75 mg,
0.5 mmol) and the mixture was kept in a refrigerator at 4 °C for 3
d, followed by stirring of the reaction mixture at room temperature
for 24 h. Solid Na2CO3 was added to the solution for 2 h, after
which the residual solid material was filtered away. The acetone
was evaporated, and the crude mixture was subjected to silica gel
chromatography to obtain 2,3-O-isopropylidene-α/β--ribofur-
anose (54 mg, 72%). The 1H and 13C NMR were in agreement with
the literature data.[15]
[1]
N. Fusetani, S. Matsunaga, Chem. Rev. 1993, 93, 1793Ϫ1806.
[2]
D. J. Faulkner, Nat. Prod. Rep. 2002, 19, 1Ϫ48 and the earlier
references in this series cited therein.
G. Rousseau, Tetrahedron 1995, 51, 2777Ϫ2849.
G. Drager, A. Kirschning, R. Thiericke, M. Zerlin, Nat. Prod.
2,3-O-Isopropylidene-L-ribitol (4): The isopropylidene derivative (6)
[3]
[4]
was dissolved in a mixture of water (5 mL) and ethanol (1 mL) and,
after the mixture had been cooled in an ice bath, a cold solution of
sodium borohydride (0.3 mmol) in water (2 mL) was added drop-
wise. After the mixture had been stirred at room temperature for
15 h, the pH was adjusted to 5Ϫ6 with acetic acid (1.7 ). The
mixture was extracted with ethyl acetate, and the combined organic
layer was washed with water, dried, and concentrated to give 4 as
a pale yellow syrup. The yield was 80%. [α]2D2 ϭ ϩ4.1 (c ϭ 0.11,
EtOH).
Rep. 1996, 13, 365Ϫ375.
M. Ishibashi, in Macrolide Antibiotics, Chemistry, Biology and
[5]
Practice, Second Edition, (Ed.: S. Omura), pp. 57Ϫ98, Elsev-
ier 2002.
[6]
H. Niwa, K. Wakamatsu, K. Yamada, Tetrahedron Lett. 1989,
30, 4543Ϫ4546.
H. Kigoshi, H. Niwa, K. Yamada, T. J. Stout, J. Clardy, Tetra-
[7]
hedron Lett. 1991, 32, 2427Ϫ2428.
H. Niwa, M. Watanabe, H. Inagaki, K. Yamada, Tetrahedron
[8]
1994, 50, 7385Ϫ7400.
D
-Oliose: After hydrolysis of mithramycin A, the sugars were meth-
[9]
H. Niwa, H. Inagaki, K. Yamada, Tetrahedron Lett. 1991, 32,
ylated[26] by use of a mixture of MeI and Ag2O and the mixture
was chromatographed (see above). The retention times of oliose
from mithramycin A were tR ϭ 7.43, 7.53, 8.34, and 8.44 min,
respectively. These values are in good accordance with data for
oliose isolated after hydrolysis of latrunculinoside B (the retention
times were tR ϭ 7.42, 7.52, 8.33, and 8.42 min, respectively).
5127Ϫ5128.
[10]
N. Lindquist, W. Fenical, Tetrahedron Lett. 1989, 30,
2735Ϫ2738.
M. S. Congreve, A. B. Holme, A. B. Hughes, M. G. Looney, J.
[11]
Am. Chem. Soc., 1993, 115, 5816Ϫ5818.
[12]
ˇ
T. Rezanka, V. M. Dembitsky, Eur. J. Org. Chem. 2002,
2400Ϫ2404.
[13]
[14]
[15]
[16]
ˇ
T. Rezanka, V. M. Dembitsky, Eur. J. Org. Chem. 2003,
Latrunculinoside A (1): Colorless powder (24.8 mg). [α]2D3 ϭ ϩ72
(c ϭ 0.13, MeOH). UV (EtOH): λmax (log ε) ϭ 307 (4.82) nm. IR
(film): ν˜max ϭ 3550 (OH), 1725 (CϭO) cmϪ1. HRFABMS: m/z ϭ
767.3779 [M ϩ H]ϩ, calcd. for [C40H59ClO12 ϩ H]ϩ 767.3776;
negative LRFABMS: m/z ϭ 765 [M Ϫ H]Ϫ, 651 [M Ϫ H Ϫ 114]Ϫ,
521 [M Ϫ H Ϫ 114 Ϫ 130]Ϫ, 391 [M Ϫ H Ϫ 114 Ϫ 2 ϫ 130]Ϫ.
NMR spectra see Table 1Ϫ3.
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