1,2-Bis(1H-indol-3-yl)ethane-1,2-dione, an Indole Alkaloid from the Marine Sponge Smenospongia sp. Matthew J. McKay, † Anthony R. Carroll, † Ronald J. Quinn,* ,† and John N. A. Hooper ‡ AstraZeneca R & D, Griffith University, Brisbane, Australia, 4111, and Queensland Museum, South Brisbane, Australia, 4101 Received July 16, 2001 1,2-Bis(1H-indol-3-yl)ethane-1,2-dione (1), a bisindole alkaloid, was isolated from the marine sponge Smenospongia sp. The known compounds indole-3-carbaldehyde (2), 6-bromoindole-3-carbaldehyde (3), and tryptamine (4) and mixtures of the (Z/E) isomers of 6-bromo-2′-demethylaplysinopsin (5a/5b) and 6-bromo-3′-deimino-2′,4′-bis(demethyl)-3′-oxoaplysinopsin (6a/6b) were also isolated. An extensive variety of indole alkaloids have been isolated from marine organisms. 1-6 In our investigations into the chemistry of marine organisms, we have isolated a variety of simple indole alkaloids from a marine sponge, including a symmetrical bisindole alkaloid. We report here the isolation and structural elucidation of the symmetrical bisindole dimer 1,2-bis(1H-indol-3-yl)ethane-1,2-dione (1) from the marine sponge Smenospongia sp (Thorectidae). Although 1 has been synthesized previously, 7-11 this is the first report on the isolation of this compound from a natural source. The known alkaloids indole-3-carbaldehyde (2), 6-bromoindole-3-carbaldehyde (3), and tryptamine (4) and mixtures of the (Z/E) isomers of 6-bromo-2′-demethyl- aplysinopsin (5a/5b) and 6-bromo-3′-deimino-2′,4′-bis(de- methyl)-3′-oxoaplysinopsin (6a/6b) were also isolated. Aplysinopsin-type alkaloids have previously been iso- lated from several marine sponges, 12,13 particularly of the family Thorectidae, 14-18 and some dendrophylliid corals. 19-22 The isolation of 1-6 provided an insight into the taxonomy of the sponge under investigation. The freeze-dried marine sponge Smenospongia sp. was exhaustively extracted with MeOH. The extract was chro- matographed on a DIOL bonded silica column using stepwise elution with i-PrOH/hexane mixtures. The frac- tion eluting with 25% i-PrOH/hexane was purified by semipreperative HPLC using DIOL bonded silica. Gradient elution afforded 6-bromoindole-3-carbaldehyde 3, 23-28 in- dole-3-carbaldehyde 2, 21,23-25,28-30 1,2-bis(1H-indol-3-yl)- ethane-1,2-dione 1, a 9:1 mixture of (Z/E) isomers of 6-bromo-2′-demethylaplysinopsin 5a/5b, 12,20 a 9:1 mixture of (Z/E) isomers of 6-bromo-3′-deimino-2′,4′-bis(demethyl)- 3′-oxo-aplysinopsin 6a/6b, 14,19 and tryptamine 4, 18,31 re- spectively. The high-resolution negative electrospray mass spectrum [(-)-HRESMS] of 1 gave a M - H + ion at m/z 287.0818, appropriate for a molecular formula C 18 H 12 N 2 O 2 . The IR spectrum contained characteristic bands at 3300 (broad, N-H) and 1605 cm -1 (strong, CdO). The 13 C NMR spectrum of 1 shows only nine signals (see Table 1). Analysis of the 13 C NMR spectrum in conjunction with DEPT and HMQC spectra indicated that four qua- ternary (189.3, 137.8, 127.0, and 114.1 ppm) and five methine carbons (137.3, 124.2, 123.1, 122.6, and 112.8 ppm) were present. The 1 H NMR spectrum of 1 (see Table 1) shows only six downfield signals, including resonances at δ 8.42 (d, J ) 7.2 Hz), 7.31 (dd, J ) 7.2, 6.1 Hz), 7.29 (dd, J ) 7.2 and 6.1 Hz), and 7.58 (m) indicative of an ortho- disubstituted benzene ring. The remaining two signals in the 1 H NMR spectrum are for an aromatic methine proton at δ 8.33 (d, J ) 3.1 Hz) and an exchangeable NH proton at δ 11.26 (br s). Consideration of the molecular formula in conjunction with the 1 H and 13 C NMR data suggested that 1 is a symmetrical dimer. A comparison of the NMR data for 1 with that of the known metabolite 2 indicated that 1 is similarly composed of a 3-substitued indole nucleus. HMBC and COSY correlations for the four aromatic methine proton signals were used to identify the connectiv- ity of the ortho-disubstituted benzene ring of the indole nucleus. Specifically, 3 J C-H HMBC correlations were ob- served from the aromatic methine protons at δ 8.42 and 7.29 to a quaternary carbon at 137.8 ppm and from the aromatic methine protons at δ 7.58 and 7.31 to a quater- nary carbon at 127.0 ppm. 3 J C-H HMBC correlations from * To whom correspondence should be addressed. Tel: 61 7 3875 6000. Fax: 61 7 3875 6001. E-mail: R. Quinn@az.gu.edu.au. † Griffith University. ‡ Queensland Museum. 595 J. Nat. Prod. 2002, 65, 595-597 10.1021/np010347v CCC: $22.00 © 2002 American Chemical Society and American Society of Pharmacognosy Published on Web 03/13/2002