UC San Diego

Two dimerized cyclic hexapeptides, antatollamides A (146) and B (147) were isolated from the colonial ascidian Didemnum molle collected in Pohnpei. The amino acid compositions and sequences were determined by interpretation of MS, 1D and 2D NMR data. Raney Ni reduction of antatollamide A cleaved the dimer to the corresponding monomeric cyclic hexapeptide with replacement of Cys by Ala. The amino acid configuration of 146 was established, after total hydrolysis, by derivatization with a new chiral reagent, (5-fluoro-2,4-dinitrophenyl)-N𝛼-L-tryptophanamide (FDTA), prepared from L-tryptophanamide, followed by LCMS analysis; all amino acids were L-configured except for D-Ala. The FDTA reagent was developed as an alternate reagent to Marfey’s reagent for the determination of the absolute configuration of amino acids. The improved resolution observed with FDTA is attributed to discrete π-cation interactions of the electron rich indole ring in Trp with the ammonium counterion in buffer. Additionally, six new cyclopentano[g]indoles, trans-herbindole A (147) and trikentramides E-I (155-159), were isolated from a West Australian sponge, Trikentrion flabbeliforme Hentschel, 1912 and their structures elucidated by integrated spectroscopic analysis. The compounds are analogs of previously described trikentrins, herbindoles and trikentramides from related Axinellid sponges. The assignment of absolute configuration of the new compounds was carried out largely by ECD – specifically, deconvolution of their Cotton effects by exploiting van’t Hoff’s principle of optical superposition – and by chemical interconversion of trans-herbindole A to trikentramide G and trikentramide G to trikentramides E, H and I.