Bioactive Bromotyrosine Alkaloids from the Bahamian Marine Sponge Aiolochroia crassa. Dimerization and Oxidative...

Nine bromotyrosine alkaloids (BTAs), including debromoianthelline (1), pseudoceratinic acid (2a), methyl pseudoceratinate (2b), 13-oxo-ianthelline (3), aiolochroiamides A-D (4a,b and 5a,b), and 7-hydroxypurealidin J (6), were isolated from a Bahamian Aiolochroia crassa (Hyatt; previously, Pseudoceratina crassa). The structures of 1-6 were established from ¹H, ¹³C, and 2D NMR spectra, IR, and mass spectrometry data. Compounds 2-4 comprise an O-methyl-2,6-dibromotyrosyl ketoxime (subunit A) amide linked to variable groups (subunit B). Compound 1 is debromoianthelline, and 2a and 2b are amides of 3-aminopropanoic acid and methyl 3-aminopropanoate, respectively. BTAs 3 and 4 are linked to 5-(2-aminoethyl)-2-iminoimidazolidin-4-one and a hexahydropyrrolo[2,3-d]imidazol-2(1H)-imine nucleus, respectively, whereas 5 is a self-dimerization motif of an aryl pyruvamide. Alkaloid 6 contains a spirocyclohexadienyl-isoxazoline-carboxamide amide coupled to 2-aminohistamine similar to that found in purealidin J and aerophobin-1 but with hydroxylation at C-7. The 2,4-diaminobutanoic acid residue in 3 was determined to be a 2:1 L- and D- mixture based on hydrolysis followed by derivatization with L-FDTA and LCMS. Diastereomeric pairs, 4a,b and 5a,b, were racemic. The relative configurations of 4a, 4b, 5a, and 5b were assigned by comparison of ¹H and ¹³C chemical shifts with those calculated by DFT. Compounds 5a,b, ningalamide B (9), and ianthelline (7) moderately inhibited butyrylcholinesterase and Candida and Cryptococcus spp.