Discovery from Hypericum elatoides and synthesis of hyperelanitriles as α-aminopropionitrile-containing polycyclic polyprenylated acylphloroglucinols

Abstract

The search for lead compounds with anti-neuroinflammatory activity from structurally ‘optimized’ natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A–D (1–4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1–4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1–5.

Patumantanes A–D, seco-Polycyclic Polyprenylated Acylphloroglucinols with Diverse Carbon Skeletons from Hypericum patulum

“…Compound 1 possessed an unusual 3,7-dioxatetracyclo[7.7.0.0 1,6 .1 11,15 ]heptadecane core based on a 1,2-seco-homoadamantane architecture. Compound 2 featured a 1,9-seco-adamantane system formed by a tricyclo [4.4.4.0.0 2,12 ]tridecane skeleton. Significantly, compounds 2 and 3 showed potential immunosuppressive activity on Con A-induced T-lymphocyte proliferation, with IC 50 values of 5.6 ± 1.2 and 11.2 ± 1.2 μM, respectively.…”

“…8−13 The adamantane and homoadamantane-types PPAPs possessed extensive biological activities, including immunosuppressive, anti-inflammatory, antitumor, antiviral, and AChE inhibitory activities, highlighting the promising application prospects of these natural metabolites. [1][2][3]14,15 Hypericum patulum is a perennial shrub widely distributed in China and often used to treat gonorrhea and hepatitis. 16,17 Previously, we have investigated the chemical constituents of H. patulum.…”

“…Patumantane A (1) possessed an unprecedented 3,7-dioxatetracyclo-[7.7.0.0 1,6 .1 11,15 ]heptadecane core based on an unusual 1,2seco-homoadamantane skeleton that was formed by the secession of C-1−C-2 linkage at the acylphloroglucinol core via retro-Claisen reaction, as well as esterification from 19− OH to C-2. Patumantane B (2) featured a 1,9-seco-adamantane ring system decorated by an unparalleled tricyclo [4.4.4.0.0 2,12 ]tridecane skeleton that was assembled by the fracture at C-1− C-9 bond through retro-Claisen, coupled with the attack from dioxatetracyclo[7.7.0.0 1,6 .1 11,15 ]heptadecane skeleton (Figure 2). In addition, the , H-33, and H 3 -37 located at the same side, assigned as α-orientation, while H-7 and H-17 were situated at β-orientation (Figure 2).…”

Abietane-Type Diterpenoids from the Arils of Torreya grandis

“…Nevertheless, chemical constituents of the arils of T. grandis have rarely been reported [13,14]. As part of our continuing search for novel and/or bioactive metabolites from Chinese medicinal plants [15][16][17], a phytochemical investigation of T. grandis arils led to the discovery of seven abietane-type diterpenoids (compounds 1-7), of which compounds 1-3 were previously undescribed, compound 4 was an unreported natural product, and compounds 5-7 were known analogs (Figure 1). Herein, the isolation, structural analysis, and bioactivities of these products are reported.…”

Three New Ionone Glycosides from Rhododendron capitatum Maxim

“…These compounds exhibit a variety of biological and pharmacological activities, including anti-inflammatory, antiviral, cytotoxic, and hypoglycaemic activities [7][8][9][10]. As part of our continuing studies on chemical components with novel structures and significant pharmacological activities from folk medicinal plants found in the Qinling region [11,12], chemical investigations of the aerial parts of R. capitatum were undertaken, leading to the isolation and identification of three new ionone glycosides (1-3) and seven known compounds (4)(5)(6)(7)(8)(9)(10). This is the first report on the sesquiterpenoid compounds from R. capitatum (Figure 1), wherein compound 1 was a novel ionone with a 6/7 bicyclic skeleton.…”