L'éponge #Plemora menoui$ (Démosponge, #O. Lithistida$, ss. #O. Trienosina$, #Desmophorina$, Fam. #Pleromidae$) récoltée à une profondeur de 500 m dans la Mer de Corail, au sud-est de Nouméa contient deux nouveaux alcaloïdes : ethyl 6-bromo-3-indolcarboxylate and 3-hydroxyacétal-6-bromoindole. (Résumé d'auteur

Duhet, D.

Guella, G.

Mancini, I.

Pietra

Richer de Forges, Bertrand

Horizon / Pleins textes

,_. , . . 
... 
Ethyl 6-Bromo-3-indolcarboxylate and 3-Hydroxyacetal-6-bromoindole, 
Novel Bromoindoles from the Sponge Pleroma menouì of the Coral Sea 
G. Guella*, I. Mancini*, D. Duhet**, B. Richer de Forges**, and F. Pietra* 
** ORSTOM, B.P. A5, Noumea, Nouvelle Caledonie 
Z .  Naturforsch. 44c, 914-916 (1989); received July 14, 1989 
Pleroma menoui, Demosponge, Alkaloids, Ethyl 6-Bromo-3-indolcarboxylate, 3-Hydroxyacetyl- 
6-bromoindole 
The demosponge Plerotna menoui (order Lithistida, suborder Trienosina (= Desmophorina), 
family Pleromidae), collected in the Coral Sea south-east of Noumea at a depth of 500 m, is 
proven here to contain the novel alkaloids ethyl 6-bromo-3-indolcarboxylate and 3-hydroxyacetyl- 
6-bromoindole. 
* Istituto di Chimica, Universith di Trento, 1-38050 Povo-Trento, Italy 
Introduction 
Indoles substituted by bromine at either C(3), 
C(5), or the non-electrophilic C(6) have been iso- 
lated from marine animals. Thus, the hemichordate 
, Ptychodera frava laysanica has given 3-bromoindole 
[l]  and 3,6-dibromoindole [2] while the sponge 
Smenospongia aurea has given 5-bromo- and 5,6-di- 
bromo-N,N-dimethyltryptamine [3]. 6-Bromoindoles 
have been isolated from the bryozoan Flustra foliacea 
[4], from the sponges Cliona celata [ 5 ] ,  Iotrochota sp. 
[6] and Aplysinopsis reticulata [7], and from scleracti- 
nian corals of the family Dendrophylliidae [8]. 
Moreover, 6-bromo-3-indolinones are products of 
prosobranch mollusks and form the basis of Tyrian 
purple [9] .  
We report here on two novel 6-bromoindoles and 
a previously known 6-bromoindole [8], isolated from 
the sponge Pleroma menoui (order Lithistida, sub- 
order Trienosina (= Desmophorina), family Plero- 
midae) from the Coral Sea. 
Results and Discussion 
The first compound isolated from the sponge was 
the less polar 1 whose spectral data suggested a 
6-bromo-3-substituted indole , [8]. The ethyl ester 
group revealed by the spectral data must thus be 
located at C(3). The structure ethyl 6-bromo-3-indol- 
carboxylate (1) for this compound was confirmed by 
oxidation of the previously available compound 3 [SI 
(which was also isolated from P. menoui as the next 
Reprint requests to Professor F. Pietra, Istituto di Chimica, 
Universith di Trento, 1-38050 Povo-Trento, Italy, telephone 
461/88 27 15. 
Verlag der Zeitschrift für Naturforschung, D-7400Tiibingen 
034 1 - 0382/89/1100- O9 14 $ O 1.3010 
. .  . 
Scheme 
1 X = O E t  
1 1 p  4 X = d O O E t  i l  
5 X=OH J 
Scheme. i) a) PCC, CH2C12; b) EtOH. ii) KMn04, 1: l  
(CH&CO-H20, room temperature, 48 h. iii) DCC, 
DMPA, EtOH, 24 h. 
more polar compound) to acid 5 which was then es- 
terified to 1 (Scheme). Before this firm structural 
proof, under the hypothesis of a weak 13C NMR 
C=O signal, we deemed structure 4 also compatible 
with the spectral data in the Experimental for the 
compound isolated from the sponge. This was ruled 
out by comparison with an authentic sample of 4 
prepared from 2 via route i as described in the 
Experimental. 
The next more polar compound isolated from this 
sponge was 2. The composition CloHsBrNOz was 
established by mass and NMR spectral analysis. Its 
indole nature, and the presence of an alcoholic func- 
tion, were revealed by its UV and IR data. Bromine 
substitution at C(6) and the carbon chain at C(3) 
were established by comparison of its NMR data 
with those for aplysinopsins [SI. The structure of the 
side-chain was confirmed by PCC oxidation of 2 and 
esterification to give 4 (Experimental). 
ORSTOM Fonds Documentaire 
G. Guella et al. Novel Bromoindoles from the Sponge Pleroma menoui 915 
Experimental 
General experimental procedures 
Melting points: Kofler hot-stage microscope. 
NMR spectra (6 values in ppm relative to internal 
Me,& (= O ppm) and J values in Hz): Varian XL-300 
spectrometer ('H at 300 MHz, "C at 75.4 MHz, J in 
Hz, multiplicities from APT [lo]. MS (EI; m/z (%)) 
home-built spectrometer based on the ELFS-4-162-8- 
Extranuclear quadrupole [ll]. UV spectra (Amax in 
nm, E in mol-' I mcm-'): Perkin-Elmer Lambda-3 
spectrophotometer. IR spectra: Perkin-Elmer 337 
spectrometer (v,,, in cm-'). Reverse-phase HPLC: 
25 x 1 cm column filled with Merck LiChroprep RP-8 
(7 nm); HPLC: 25 x 1 cm column filled with Merck 
LiChrosorb Si-60 (7 nm), UV monitoring at 254 nm, 
solvent flux 5 ml min-'. Flash chromatography: 
Merck Kieselgel 60, 15-25 nm. TLC: Merck Sim5,, 
plates. 
Collection and isolation 
The sponge was collected by dredging in Sep- 
tember 1985 south-east of Noumea at a depth of 
500 m and was identified by Professor C. Levi. The 
fresh sponge was lyophilized and then extracted with 
80% EtOH. The extract was partly evaporated and 
then partitioned between water and CHzCIz. The or- 
ganic layer was evaporated to dryness to leave a dark 
sticky residue (1.18 g) which was subjected to flash 
chromatography on 20 g of Sioz with hexane/AcOEt 
gradient elution, collecting 20 fractions of 50 ml 
each. The sixth fraction was evaporated and the resi- 
due was subjected to reverse-phase HPLC with 
CH3CN/H20 62/38 obtaining pure 1 (15 mg) at tR = 
8.2 min. Similar work-up of the ninth flash-chro- 
matographic fraction with CH3CN/H20 42/58 led to 
pure 3 (32 mg, tR = 9.3 min). 
Flash-chromatographic fractions 13 and 14 were 
evaporated and then first subjected to reverse-phase 
HPLC with CH3CN/H20 3j7 and then the fraction 
containing product 2 was further subjected to HPLC 
with hexane/AcOEt 1/3 to give pure 2 (12 mg, fR = 
7.1 min). 
H-C(S)), 7.74 (dd, J = 1.8, 0.6, H-C(7)), 4.32 (9, 
J = 7.2, 2H-C(2')), 1.37 (t, J = 7.2, 3H-C(3')). 
13CNMR ((CD3)zCO) 6 133.28 (d, C(2)), 130.84 
(s, C(3)), 126.11 (s, C(3a)), 123.42 (d, C(4)), 125.25 
(d, C(5)), 116.41 (s, C(6)), 115.86 (d, C(7)), 138.47 
(s, C(7a)), 164.90 (s, C(l')), 60.00 (t, C(2')), 14.84 ' 
(9, C(3')). MS: 269-267 (45, M+*), 241-239 (27, 
M+'-28), 224-222 (100, M+.-OCH2CH,). 
Synthesis of ethyl 6-bromo-3-indolcarboxylate (1) 
6-Bromoindol-3-carboxaldehyde (3) [8] (9 mg, 
0.04 mmol) in 2 ml of 1:l acetone-water was added 
of KMn04 [12] (8 mg, 0.05 mmol). After 48 h of stir- 
ring at room temperature, TLC indicated the com- 
plete disappearance of 3 from the mixture which was 
filtered on silica gel. Crude 5, obtained by evapora- 
tion of the filtrate, was dissolved in 2 ml of EtOH and 
added of 1,3-dicyclohexylcarbodiimide (10.3 mg, 
0.05 mmol) and of 4-dimethylaminopyridine (6.1 mg, 
0.05 mmol) [13]. The mixture was stirred at room 
temperature for 24 h and then filtered and evapo- 
rated. The residue was subjected to preparative silica- 
gel TLC with 2:3 hexane-AcOEt to give 3.2 mg of 
pure 1 with physical data identical to those of the 
natural product. 
Synthesis of the ethyl ester of 
6-bromo-3-indolglyoxylic acid (4) 
3-Hydroxyacetyl-6-bromoindole (2) (5 mg, 
0.02 mmol) was stirred with 6 molar equivalents of 
PCC in 1 ml of CH2C12, whereby all 2 disappeared. 
The mixture was added of 2 ml of EtOH and, after 
1 h, it was filtered on silica gel Si-60 (15-25 km). 
The filtrate was evaporated and the residue was sub- 
jected to HPLC with hexane/AcOEt 3/2 to give 
1.8 mg of pure 4 (tR = 6.1 min). M:p. 240-242 "C 
(lit. [14] 241-242 OC). 'H NMR ((CD3)&O) 6 11.48 
(br. s, NH), 8.50 (br. s, H-C(2)), 8.23 (d, J = 8.5, 
H-C(4)), 7.45 (dd, J = 8.5, 1.9, H-C(5)), 7.70 (d, 
J = 1.8, H-C(7)), 4.39 (9, J = 7.2, 2H-C(3')), 1.38 
(t, J = 7.2; 3H-C(4')). 
3-Hydroxyacetyl-6-bromoindole (2) 
Colorless microcrystalline powder, m.p. 
194-196°C (MeOH). UV A,, 293 (9200), 265 
(12200), 242 (13100), 217 (24100); IR (KBr) 3420s, 
(br. s, NH), 8.34 (d, J = 2.9, H-C(2)), 8.20 (dd, 
3250~, 1650~, 1635s; 'H NMR ((CD&CO) 6 11.29 
J =  8.4,0.6,H-C(4)),7.37(dd,J=8:4,1.8,H-C(5)), 
Ethyl 6-bromo-3-indolcarboxylate (1) 
Colorless micrmxystalline powder, map. 
147-149 "C (MeOH). 'H NMR ((CD3)zCO) 6 11.09 
(br. s, NH), 8.04 (d, J = 2.8, H-C(2)), 8.05 (dd, 
J = 8.5, 0.6, H-C(4)), 7.34 (dd, J = 8.5,'1.8, 
916 
I .  
G. Guella et al. Novel Bromoindoles from the Sponge Pleroma menouì 
7.74 (dd,J = 1.8,0.6, H-C(7)), 4.71 (s, 2H-C(2')). 13C Acknowlednements 
NMR ((CD&CO) 6 134.16 (d, C(2)), 114.41 (s, 
C(3)), 125.58 (s, C(3a)), 123.92 (d, C(4)), 125.94 (d, 
C(5)'), 116.96 (s, C(6)), 115.83 (d, C(7)), 138.44 (s, 
C(7a)), 194.59 (s, C(l')), 66.00 (t, C(2')). MS: 
255-253 (9, M'.), 224-222 (100, Mt*-CH20H), 
196-194 (20, MSs-C0CH2OH). 
- 
We thank Professor C. Levi of the Laboratoire de 
Biologie des InvertCbrCs Marins et Malacologie, 
Museum National d'Histoire Naturelle, Paris, for the 
sponge identification. This work has been carried out 
' within the framework of the collaborative program 
ORSTOM-CNRS on Marine Substances of Biologi- 
cal Interest. The work in Trento has been supp0rte.d 
by MPI (Progetti di Interesse Nazionale) and CNR 
(Roma). . 
[l]  T. Higa and P. J. Scheuer, in: Marine Natural Prod- 
ucts Chemistry (D. J. Faulkner and W. H. Fenical, 
eds.), pp. 35-43, Plenum Press, New York 1977. 
[2] T. Higa, R. K. Okuda, M. Severns, P. J .  Scheuer, 
Cun-Heng He, X. Changfu, and J. Clardy, Tetra- 
hedron 43, 1063 (1987). 
[3] A. A. Tymiak, K. L. Rinehart, Jr.,  and G. J. Bakus, 
Tetrahedron 41, 1039 (1985). 
[4] P. Wulff, J. S .  Carl& and C. Christophersen, J. Chem. 
Soc., Perkin Trans. 1,2895 (1981). 
[5] R. J. Andfersen, Tetrahedron Lett. 1978, 2541. 
[6] G. Dellar, P. Djura, and M. V. Sargent, J. Chem. 
Soc., Perkin Trans. 1, 1679 (1981). 
[7] R. Kazlauskas. P, T. Murphy, R. J. Quinn, and R. J. 
Wells, Tetrahedron Lett. 1977, 61. 
[8] G. Guella, I. Mancini, H, Zibrowius, and F. Pietra, 
Helv. Chim. Acta 71, 773 (1988). 
[9] G. Prota, in: Marine Natural Products. Chemical and 
Biological Perspectives, Vol. III (P. J .  Scheuer, ed.), 
pp. 159-164, Academic Press, New York 1980. 
[lo] S, L. Patt and J. N. Shoolery, J. Magn. Reson. 46,535 
(1982). 
[ l l ]  A. Slomp, G. Chiasera, C. Mezzena, and F. Pietra, 
Rev. Sci. Instr. 57, 2786 (1986). 
[12] D. H. R. Barton, R. B. Boar, and D. A. Widdowson, 
J ,  Chem. Soc. C 1970, 1208. 
[13] A. Hassner and V. Alexanian, Tetrahedron Lett. 
1978, 4475. 
[14] A.'Da Settimo, M. F. Saettone, E. Nannipieri, and P. 
Barili, Gazz. Chim. Ital. 97, 1304 (1967). 
f 
I 


Ethyl 6-Bromo-3indolcarboxylate and 3-Hydroxyacetal-6-bromoindole, novel bromoindoles from the sponge Pleroma menoui of the Coral Sea

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