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

Abstract

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.

Keywords

• mangrove
• Xylocarpus moluccensis
• limonoid
• xylomolins
• skeletal diversity
• antitumor
• anti-HIV