Structure Revisions of the Sponge-Derived Dibrominated Bis-indole Alkaloids, Echinosulfone A and the Echinosulfonic Acids A to D

• Published in: Journal of organic chemistry 2020-03, Vol.85 (5), p.3490-3496
• Main Authors: Holland, Darren C, Kiefel, Milton J, Carroll, Anthony R
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b03221

The structures of the sponge-derived dibrominated bis-indole alkaloids, namely, echinosulfone A (2) and the echinosulfonic acids A to D (9–12), have been revised based upon reanalysis of their NMR spectroscopic and MS spectrometric data, comparison of this data with those reported for structurally related compounds, and based on their common biogenesis. The reinterpreted spectroscopic evidence has been corroborated by the total synthesis of the revised structure of echinosulfone A (2). This was achieved by bis-carbonylation at C-3 of the magnesium salt of 6-bromoindole with triphosgene to afford the new dibrominated bis-indole ketone, bis­(6-bromo-1H-indol-3-yl)­methanone (3), followed by N-sulfonation of one indole moiety to furnish 6-bromo-3-(6-bromo-1H-indole-3-carbonyl)-1H-indole-1-sulfonate (2). The five marine alkaloids corrected herein each contain an indole sulfamate and are all carbon-bridged dibrominated bis-indoles: echinosulfone A (2) is a di­(1H-indol-3-yl)­methanone, while the echinosulfonic acids A to D (9–12) are methyl 2,2-bis­(1H-indol-3-yl) acetates.