Three novel bromo-compounds have been isoZated from the sponge Veerongia aerophoba. The sponge previous7.y identified as V. aerophoba, containing related but different bromocompounds, was indeed the related spezes V. cavernicola. -Two species of Veerongia genus sponges are widespread along the Italian coasts': Verongia aerophoba (= ApZysina aerophoba Schmidt, 18 6 2) and Verongia cavernico Za Vacelet, 1959. A number of interesting new metabolites were identified3 from a sponge collected in the bay of Naples area and reported as Veerongia aerophoba in the chemical papers. However direct comparison4 of this sponge with the true Verongia aerophoba, eventually collected from the area near Gallipoli, has shown the previously examined sponge to be the related species Verongia cavernicoZa. We report now that the true sponge Verongia aerophoba contains several new bromo-compounds, along with some others previously isolated from Verongia cavernice Za .V. aerophoba (800 g, dry weight after extraction) was extracted with acetone. The extract was evaporated under reduced pressure and the resulting aqueous suspension was extracted sequentially with diethyl ether and n-butyl alcohol.The ethereal extract (22.5 g) was chromatographed on a silica gel column with CHC13 and increasing amounts of CH,OH to afford inter alia the dienone l5 (0.27 g), aeroplysinin-1 (2)6 (0.38 g), both previously isolated from V. cavernicola and other Veerongia species, and the new compound 3a (0.97 g) which was proved to be isomeric with fistularin-3' and accordingly named isofistularin-3.Isofistularin-3, C31H30 Br6NhOll, [a] + 108' (2.75, CH,OH), shows IR and UV D absorptions practically identical with those reported for fistularin-3'. Acetylation of 3a (AczO, Py, reflux) gave a crystalline tetraacetate (3b), m.p. 194-97'C k]D + 132' (1.6, CHCl,), whose 270 MHz 'H-NMR spectrum shows minor but significant differences when directly compared with the spectrum of fistularin-3 tetraacetate':protons Ha and Ha' show two distinct signals in the spectrum of 3b at 6 5.82 and 5.86, while in the spectrum of fistularin-3 tetraacetate a unique broad singlet (2H) at 6 5.86 was observed; the signals due to the methylene protons of the two isoxazole rihgs were centred at 6 3.09 (2H), 3.41 and 3.46 in 3b, while the same protons resonate at 3.06, 3.08, 3.45 and 3.47 in the spectrum of fistularin-3 tetraacetate.Treatment of 3b with methanolic KOH afforded a phenol (4a),FAB-mass spectrum' 1109, 1111, 1113, 1115, 1117, 1119, 1121 (MH+), which on reacetylation gave 4b whose 270 MHz 'H-NMR spectrum is indistinguishable from the spectrum reported6 for the analogous compound obtained by similar treatment of fistularin- -3 tetraacetate.From these data it is argued that 3a is isomeric with fistularin-3, the difference between the two compounds lying in the stereochemistry of one (or more) of the chiral centres.The butanolic extract (7.9 g) gave some polar compounds. From this mixture the purification of two new bromo-compounds, aerophobin-1 (5a) and -2 (8a), was achieved by a multiple-step procedure including chromatography on Sephadex LH-20 (CH,OH) and silica gel (CHC13-CH30H).The less polar compound, aerophobin-1 (5a; 0.25 g), C15H16N404Br2, FAB-mass spectrum9 475, 477, 479 (MH+), ia] D+ 187' (2.0, CHsOH), has a very simple 'H-NMR spectrum" in which, besides the readily assigned signals"" due to the spirocyclohexadienylisoxazole moiety, there are two triplets at 6 3.67 and 2.99 and two singlets at 6 6.85 and 7.59 which suggest, in conjunction with the elemental composition of the molecule, the presence of a histamine residue.Acetylation (AczO, Py; r.t.) afforded a crystalline monoacetyl derivative 5b, m.p. 164-67'C, FAB-mass spectrum 517, 519, 521 (MH+), whose 13C-NMR spectrum (Table) when compared with the spectrum of the acetyl derivative (6) of the previously isolated aerothionin", which is the major bromo-compound of V.cavernicoZa and is absent in the extracts of V. aerophoba, confirmed the presence of the spirocyclohexadienylisoxazole moiety. Hydrolysis of 5a (6N HCl; reflux) afforded histamine (7) confirming the structure of aerophobin-1 as 5a.The more polar compound, aerophobin-2 (8a; 0.67 g), C16H19N504Brzr FAB-mass spectrum 504, 506, 508 (MH+), [cx],+ 139' (1.9, CH30H), displays a ' H-NMR 12 spectrum similar to that of 5a, the major differences lying in the presence of an additional methylene signal at 6 2.01 and in the absence of the C-2' proton signal of the imidazole residue.Acetylation of 8a with acetic anhydride and pyridine affords a diacetate with cannot be purified chromatographically from a persistent contaminant. However, acetylation of 8a with acetic anhydride/pyridine in acetic acid (5-fold excess) at r.t., afforded the monoacetate 8b in good yields, which was successfully purified by conventional silica gel chromatography. Also in this case the 13C-NMR spectrum (Table) confirmed the presence of the spirocyclohexadienylisoxazole moiety; hydrolysis of 8a (6N HCl; reflux) yielded 2-amino-homoistamine (9), identified bycomparison with an authentic sample13. 9 could be linked in aerophobin-2 through either the C-2' and the side chain amino groups: however, the chemical shift of C-IO in the "C-NMR'spectrum of Bb (Table), very close to the value of the corresponding carbon in the spectrum of aerothionin acetate (6), strongly suggests the arrangement reported in 8a-b. Isofistularin-3 (3a) is cytotoxic in vitro (KB cells), the effective dose being 4 pg/ml.