Twenty-Nine New Limonoids with Skeletal Diversity from the Mangrove Plant, Xylocarpus moluccensis

Twenty-nine new limonoids-named xylomolins A₁-A₇, B₁-B₂, C₁-C₂, D-F, G₁-G₅, H-I, J₁-J₂, K₁-K₂, L₁-L₂, and M-N, were isolated from the seeds of the mangrove plant, Xylocarpus moluccensis. Compounds 1-13 are mexicanolides with one double bond or two conjugated double bonds, while 14 belongs to a small group of mexicanolides with an oxygen bridge between C1 and C8. Compounds 15-19 are khayanolides containing a Δ8,14 double bond, whereas 20 and 21 are rare khayanolides containing a Δ14,15 double bond and Δ8,9, Δ14,15 conjugated double bonds, respectively. Compounds 22 and 23 are unusual limonoids possessing a (Z)-bicyclo[5.2.1]dec-3-en-8-one motif, while 24 and 25 are 30-ketophragmalins with Δ8,9, Δ14,15 conjugated double bonds. Compounds 26 and 27 are phragmalin 8,9,30-ortho esters, whereas 28 and 29 are azadirone and andirobin derivatives, respectively. The structures of these compounds, including absolute configurations of 15-19, 21-23, and 26, were established by HRESIMS, extensive 1D and 2D NMR investigations, and the comparison of experimental electronic circular dichroism (ECD) spectra. The absolute configuration of 1 was unequivocally established by single-crystal X-ray diffraction analysis, obtained with Cu Kα radiation. The diverse cyclization patterns of 1-29 reveal the strong flexibility of skeletal plasticity in the limonoid biosynthesis of X. moluccensis. Compound 23 exhibited weak antitumor activity against human triple-negative breast MD-MBA-231 cancer cells with an IC50 value of 37.7 μM. Anti-HIV activities of 1, 3, 8, 10, 11, 14, 20, 23-25, and 27 were tested in vitro. However, no compounds showed potent inhibitory activity.