Leptoclinidamines A-C, Indole Alkaloids from the Australian Ascidian Leptoclinides durus

Three new indole alkaloids, leptoclinidamines A-C (1-3), were isolated from the Australian ascidian Leptoclinides durus. Their structures were determined by analysis of 2D NMR spectra. Leptoclinidamines A and B both contain an indoleglyoxylic acid attached to an L-arginine. The structure of leptoclinidamine A was confirmed by total synthesis. Leptoclinidamine C contains the naturally rare 1,3-dimethyl-5-(methylthio)histidine attached to a 6-bromoindole-3-carboxylic acid. Leptoclinidamine C (3) and both enantiomers of leptoclinidamine A (1) were tested for antimalarial, anti trypanosomal, and cytotoxic activity, but none of the compounds were bioactive.