Cyclic Hexapeptide Dimers, Antatollamides A and B, from the Ascidian Didemnum molle. A Tryptophan-Derived Auxiliary for l- and d-Amino Acid Assignments

Abstract

Two dimerized cyclic hexapeptides, antatollamides A (1) and B (2), were isolated from the colonial ascidian Didemnum molle collected in Pohnpei. The amino acid compositions and sequences were determined by interpretation of MS and 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 1 was established, after total hydrolysis, by derivatization with a new chiral reagent, (5-fluoro-2,4-dinitrophenyl)-N-l-tryptophanamide (FDTA), prepared from l-Trp, followed by LCMS analysis; all amino acids were found to be l-configured except for d-Ala.

Genome‐Based Identification of a Plant‐Associated Marine Bacterium as a Rich Natural Product Source

“…The absolute configuration of amino acids was determined by Marfeysanalysis, [19] using the acid hydrolysate of 3 and of its dethio derivative generated by reaction with Raney nickel (Figure S34). [20] Thea mino acids in 3 were assigned to be d-Phe and two l-Cys,w hich is in good agreement with the predicted stereochemistry based on the presence of an…”

Marine natural products

“…The metabolites reported in 2017 included carbamates 1428-1431, ureas 1432-1435 and isoquinoline 1436 (Didemnum molle), 656 isoquinoline-quinones 1437-1439 (Ascidia virginea), 657 antibacterial cadiolides J-M 1440, 1441-1443 (Pseudodistoma antinboja), 658 new congeners in the mandelalide series 1444-1450 (Lissoclinum mandelai), 659 cytotoxic bistratamides M and N 1451, 1452 (L. bistratum), 660 and cyclic hexapeptide dimers antatollamides A 1453 and B 1454 (D. molle). 661 The absolute conguration of the constituent amino acids of antatollamide A were secured by making use of a new tryptophan-based chiral derivatisation reagent.…”

“…The nding that antiproliferative potency observed in biological assays depends upon the oxidative phenotype of the cell line in question, and that this phenotype can vary with cell density, provides an explanation for the previously reported disparities noted for synthetic-sourced mandelalide A. Antatollamides A 1453 and B 1454 are unusual dimeric cyanobactins, apparently the rst such examples that embody intermolecular dimerisation through cysteine. 661 The two structures differ in the S-trans/ S-cis congurations of the proline residues.…”

Genome‐Based Identification of a Plant‐Associated Marine Bacterium as a Rich Natural Product Source

“…Thel ength of the fatty acid chain was determined by ESI-MS 2 analysis ( Figures S31B and S32), and the connection of each component was deduced from ROESY data ( Figures S31C and S33). [20] Thea mino acids in 3 were assigned to be d-Phe and two l-Cys,w hich is in good agreement with the predicted stereochemistry based on the presence of an The absolute configuration of amino acids was determined by Marfeysanalysis, [19] using the acid hydrolysate of 3 and of its dethio derivative generated by reaction with Raney nickel ( Figure S34).…”