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

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 1 H, 13 C, 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(1 H )-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 1 H and 13 C chemical shifts with those calculated by DFT. Compounds 5a , b , ningalamide B ( 9 ), and ianthelline ( 7 ) moderately inhibited butyrylcholinesterase and Candida and Cryptococcus spp.