Polycyclic Polyprenylated Acylphloroglucinols Bearing a Lavandulyl-Derived Substituent from Garcinia xanthochymus Fruits

Abstract

Many type B polycyclic polyprenylated acylphloroglucinols (PPAPs) bear a lavandulyl-derived substituent, and the configurational assignment of this side chain can be difficult and sometimes leads to erroneous conclusions. In this study, 21 PPAPs, including the new xanthochymusones A–I (1–9), have been isolated from the fruits of Garcinia xanthochymus and structurally characterized. The relative configuration of the C-30 stereocenter was assigned by a combination of chemical transformations, 1H–1H coupling constants, conformational analysis, and NOE experiments. The configurational assignment of compound 7 indicates that the relative configuration at C-30 of PPAPs is not always the same. The absolute configurations of the new compounds were assigned by ECD and X-ray diffraction data, as well as by biosynthetic considerations. Analysis of NMR data enabled the configurational revision of garcicowins C and D. All the isolated PPAPs were tested for antiproliferative activity against three human hepatocellular carcinoma cell lines, including Huh-7, Hep 3B, and HepG2. Compounds 5 and 6, 7-epi-isogarcinol (16), and coccinone C (17) exhibited moderate antiproliferative activity. Compounds 6 and 16 induced apoptosis and inhibited cell migration in Huh-7 cells, probably through downregulating the STAT3 signaling pathway. This study provides effective methods for configurational assignments of type B PPAPs.

Structure Revision of Type B Polycyclic Polyprenylated Acylphloroglucinols Fused to a Partly Reduced Furan Ring

“…We have had a long-standing interest in confirming or correcting proposed structures of natural PPAPs and have corrected the structures of dozens of them, ,,− so we decided to reinvestigate the assigned structures of UF, UG, AE, AF, UK, UO, and SA–SD. First, we reisolated furan-fused PPAPs UG, AE, and AF from Hypericum patulum .…”

Cytotoxic Isopentenyl Phloroglucinol Compounds from Garcinia xanthochymus Using LC-MS-Based Metabolomics

“…Previous studies showed that the polyprenylated benzophenones (belonging to PPAPs) isolated from G. xanthochymus fruits displayed potent cytotoxicity in different human cancer cell types [ 32 , 33 , 34 ]. Recently, 9 new and 12 known PPAPs were isolated from G. xanthochymus fruits, and 4 PPAPs showed moderate inhibitory activities against 3 hepatocellular carcinoma cell lines with IC 50 values in the range of 3.9 to 17.3 μM [ 35 ]. However, the fruit extract of G. xanthochymus in our study had no significant cytotoxic effect on five cancer cell lines.…”

Total synthesis and structural reassignment of garcinielliptone FC, a polycyclic polyprenylated acylphloroglucinol with diverse bioactivity

“…23 However, the reported NMR data of GFC (Tables S1 and S2, ESI †) are not consistent with a type A structure according to our systematic study of structural confirmations of PPAPs. [24][25][26][27][28][29] Specifically, its C-1 chemical shift (d C 69.1) is much lower than that of type A PPAPs (about 80 ppm) but more consistent with that of type B structures (about 70 ppm). [29][30][31] Furthermore, almost all the reported PPAPs carrying a lavandulyl-derived substituent such as 2-isopropenyl-5-methyl-5-hexenyl (isolavandulyl) have type B structures, with this substituent located at the C-5 position, not the C-7 position as in GFC.…”

“…[24][25][26][27][28][29] Specifically, its C-1 chemical shift (d C 69.1) is much lower than that of type A PPAPs (about 80 ppm) but more consistent with that of type B structures (about 70 ppm). [29][30][31] Furthermore, almost all the reported PPAPs carrying a lavandulyl-derived substituent such as 2-isopropenyl-5-methyl-5-hexenyl (isolavandulyl) have type B structures, with this substituent located at the C-5 position, not the C-7 position as in GFC. 23 If one swaps the 3,4-dihydroxybenzoyl and prenyl groups at C-1 and C-3 of GFC, and the isolavandulyl and prenyl groups at C-7 and C-5 of GFC, respectively, GFC is converted to xanthochymol (2), 32 a type B PPAP showing a very small difference with the wellknown compounds garcinol/guttiferone E (3/4) (Fig.…”