X-ray crystallography and unexpected chiroptical properties reassign the configuration of haliclonadiamine

Haliclonadiamine and papuamine are bis-indane marine natural products isolated from the marine sponge Haliclona sp. Their relative structures were previously reported to differ by inversion at only one of their eight shared stereo-centers. Here X-ray crystallography shows the opposite to be true: papuamine has a 1R,3S,8R,9S,14S,15R,20S,22R configuration while haliclonadiamine has a 1S,3R,8S,9R,14R,15S,20R,22R configuration. Paradoxically the ECD of each structure displays a negative Cotton effect. X-ray crystallography reveals the two structures adopt similar conformations of their 13-membered macrocyclic core that comprises a configurationally relevant diene. B97x-D/Def2-TZVPP-(MeOH)-calculated ECD supports the diene configuration with the macrocycle dominating the ECD Cotton effect for haliclonadiamine and papuamine. Additional crystallographic and chiroptical analysis of three sponge samples from geographically distant locations indicate this pair of natural products always exists as a configurationall...