Structural Revision of Hyperibrin B and Hyperscabrones H and I by Biosynthetic Considerations, NMR Analysis, and Chemical Synthesis

Abstract

Previously, Gao et al. reported the isolation and structural determination of three natural products, hyperibrin B (HB), hyperscabrone H (HH), and hyperscabrone I (HI), from Hypericum scabrum. HB and HH had different NMR spectroscopic data, but they were assigned identical structures. Furthermore, these compounds should be derived from bicyclic polyprenylated acylphloroglucinols (BPAPs) via degradation, but the assigned structural features of the prenyl and prenylmethyl groups being cis and meta-substituted on the cyclohexanone core were not consistent with their biosynthetic origin. In this note, we revise the structures of HB, HH, and HI via NMR and MS spectroscopic analyses and biosynthetic considerations. We also complete a total synthesis of the revised structure of HB as well as its analogue, hyperibrin A, to further confirm the revision. The revised structures of HB, HH, and HI have not been reported.

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 .…”

“…However, C-7 of SA is allylic due to the unusual oxidation pattern of the C-7 substituent, so the Grossman–Jacobs rule should not be applied here. The prenyl-derived group at C-7 and the prenylmethyl group at C-8 of SA are biosynthetically derived from a geranyl group, , which has a trans double bond, and these two groups are trans to one another in all PPAPs determined to have prenylmethyl groups at C-8, so we confidently correct the configuration of C-7 in SA to exo.…”

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.…”

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

“…Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of structurally fascinating hybrid natural products that are found only in plants of the families Hypericaceae and Clusiaceae and exhibit a broad range of biological activities. , To date, more than 1000 PPAPs with diverse structures have been characterized. − As we have a long-standing interest in the investigation of structures and bioactivities of PPAPs, − we selected the fruit of Garcinia xanthochymus for further investigation. G. xanthochymus , commonly known as yellow mangosteen and gamboge, is a rich source of PPAPs with antioxidant, anti-inflammatory, and anticancer activities. − Our systematic phytochemical investigation of the dried fruits has led to the isolation and structural characterization of 21 type B PPAPs that bear a substituent derived from a lavandulyl (2-isopropenyl-5-methyl-4-hexen-1-yl) group at C-8, including the new xanthochymusones A–I ( 1 – 9 ).…”