Leucascine, a β-alkylpyridine from the Okinawan sponge Leucascus protogenes

A new β-alkyl pyridine alkaloid, leucascine (1), was isolated from the Okinawan marine sponge Leucascus protogenes. Its planar structure was elucidated using a combination of 1D and 2D NMR spectroscopy, mass spectrometry, and comparison with reference compounds. The configuration at the stereogenic centre C-2 was determined through Mosher’s method using MPA derivatives (compounds 2 and 3), supported by the analysis of 1H NMR chemical shifts. To validate this assignment, model compounds 7 and 8 were synthesised and subjected to density functional theory (DFT) calculations. Conformational analysis revealed that both enantiomers favour the anticlinal-E (ac-E) conformation, and the computed chemical shifts closely matched the experimental data, further confirming the possibility of the 2S configuration of leucascine (1). Notably, compound 1 demonstrated significant cytotoxicity, exhibiting an IC50 value of 9.2 µM against NBT-T2 tumour cells.