A new bis-1-oxaquinolizidine alkaloid, 3a-methylaraguspongine C [1], and four known bis-1-oxaquinolizidines, araguspongines C [2], D [3], and E [4], and xestospongin D [5], have been isolated and characterized by spectroscopic methods from the sponge Haliclona exigua. In continuation of our studies on marine organisms for biologically active secondary metabolites, we have examined the sponge Haliclona exigua (Kirkpatrick), collected at Chidiatapu, Andaman Islands, during March 1992. A literature survey revealed that the genus Haliclona produces complex macrocyclic alkaloids, including the β-carboline-derived oncolytic alkaloids manzamines A, B, and C (1,2), and the pentacyclic alkaloids ppuamine (3) and haliclonadiamine (4), which have antifungal and antimicrobial properties. The ¹H- and ¹³C-nmr spectra of a defatted crude extract revealed that Haliclona exigua contained bis-1-oxaquinolizidine alkaloids. The presence of these vasodilatory alkaloids in Xestospongia sp. has been reported in previous publications (5-8). Freeze-dried specimens (400 g) were extracted successively with n-hexane, EtOAc, and MeOH at room temperature. The crude EtOAc extract showed moderate antibacterial activity at 200 μg/disk on Bacillus subtilis (2 mm zone of inhibition), Pseudomonas fluorescence (5 mm), Escherichia coli (7 mm), and Klebsiella pneumoniae (7 mm). This extract was subjected to column chromatography (cc) on Sephadex LH-20 (CH₂Cl₂-MeOH, 1:1) and Si gel to afford four known bis-1-oxaquinolizidine alkaloids, araguspongines C [2], D [3], E [4], and xestospongin D [5], and a new bis-1-oxaquinolizidine, 3a-methylaraguspongine C [1]. Compounds 2-5 were characterized by comparing physico-spectral data with reported values (5,7). Compound 1 (5 mg) was obtained as an amorphous solid with [α]ᴅ +1.2° (c=0.15, CHCl₃) and analyzed for C₂₉H₄₂N₂O₄. Its ir spectrum showed a peak at 3498 cm⁻¹ indicating the presence of a hydroxyl group and no Bohlmann bands, suggesting the absence of a trans-quinolizidine system (9). The ¹H- and ¹³C-nmr spectra of compound 1 showed close similarities with those of araguspongine C [2]. Particularly diagnostic were the H-10 and H-10' signals at δ 4.03 (1H, s) and 4.06 (1H, s), due to effects of the lone-pair electrons of the tertiary nitrogens (10,11). Further, the ¹H-nmr spectrum of 1 showed the presence of a secondary CH₃ group at δ 0.68 (3H, d, J=6.5 Hz in CDCl₃) (δ 0.51, d, J=6.5 Hz in C₆D₆). The position of this secondary CH₃ group was deduced by direct comparison with xestospongin B [6] in which the Me-3 group resonated at δ 0.51 in C₆D₆ (5). The ¹³C-nmr chemical shifts of the bottom half of the molecule of compound 1 were almost identical to those of araguspongine C [2] and Me-3, C-2, and C-4 resonated at δ 14.62, 82.6, and 60.34, respectively, comparable with analogous data for xestospongin B [6] (Table 1) (5). From the foregoing spectral data, the relative stereochemistry of compound 1 was assigned as 3a-methylaraguspongine C. To our knowledge this is the first instance of the isolation of bis-1-oxaquinolizidines from Haliclona sp.