Hyperbenzones A and B, two 1,2-seco and rearranged polycyclic polyprenylated acylphloroglucinols from Hypericum beanii

• Published in: Chinese chemical letters Vol. 33; no. 8; pp. 4121 - 4125
• Main Authors: Lu, Weijia, Zhang, Yanqiu, Li, Yawei, Ye, Shengtao, Luo, Jun, Kong, Lingyi, Xu, Wenjun
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2022; Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 210009,China
• Subjects: 1,2-seco-Bicyclic derivatives; Hyperbenzones A and B; Hypericum beanii; NASH; seco-PPAPs; 1,2-seco-Bicyclic derivatives; seco-PPAPs; Hypericum beanii; Hyperbenzones A and B; NASH
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2021.11.011

Two novel seco-polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbenzones A (1) and B (2), were isolated from the roots of Hypericum beanii, together with one known biosynthetic congener 3. Compound 1 incorporates a 6/5/5 ring system with an unprecedented spiro[bicyclo[3.3.0]octane-3,1ʹ-cyclohexane]-2,2ʹ‑dione motif. The structures of 1 and 2 were determined by a combination of high resolution electrospray ionization mass spectroscopy (HRESIMS), nuclear magnetic resonance (NMR) spectroscopic analyses, gage-independent atomic orbital (GIAO) NMR chemical shift calculation with DP4+ analyses, electronic circular dichroism (ECD) calculation, and X-ray diffraction analysis. A 1,2-seco retro-Claisen rearrangement from a bicyclo[3.3.1]nonane PPAP precursor and following chemodivergent radical cascade cyclizations are proposed as the key steps in the biosynthetic pathway to yield compounds 1 and 2. Biological investigations indicated that compounds 1 and 3 could decrease intracellular lipid accumulation in a palmitic acid-induced nonalcoholic steatohepatitis (NASH) cell model. [Display omitted] Unprecedented 1,2-seco-bicyclo[3.3.1]nonane-derived polycyclic polyprenylated acylphloroglucinol (PPAP) with a unique spiro[bicyclo[3.3.0]octane-3,1ʹ-cyclohexane]-2,2ʹ‑dione framework, hyperbenzone A (1), along with a new congener hyperbenzone B (2), were isolated from Hypericum beanii.