X‑ray Crystallography and Unexpected Chiroptical Properties Reassign the Configuration of Haliclonadiamine

• Published in: Journal of the American Chemical Society Vol. 142; no. 6; pp. 2755 - 2759
• Main Authors: Liu, Hong-Bing, Imler, Gregory H, Baldridge, Kim K, O’Connor, Robert D, Siegel, Jay S, Deschamps, Jeffrey R, Bewley, Carole A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.02.2020; Amer Chemical Soc
• Subjects: Alkaloids - chemistry; Chemistry; Chemistry, Multidisciplinary; Crystallography, X-Ray - methods; Magnetic Resonance Spectroscopy - methods; Molecular Structure; Optics and Photonics - methods; Physical Sciences; Science & Technology; (+)-PAPUAMINE; PAPUAMINE; (-)-PAPUAMINE; MARINE SPONGE; ALKALOIDS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.9b12926

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 stereo­centers. 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 analyses of three sponge samples from geographically distant locations indicate this pair of natural products always exists as a configurationally related couple. The co-discovery of a biosynthetic precursor, halichon­driamine C, present in these same Haliclona samples must be considered when discussing any biosynthetic pathway. Taken together, this work justifies a reassignment of haliclona­diamine’s structure and opens the question of how this complex stereo­chemical relationship between haliclona­diamine and palauamine arises biosynthetically.