Dibenzocyclooctadiene lignans from the family Schisandraceae: A review of phytochemistry, structure-activity relationship, and hepatoprotective effects.

Liver injury is a common pathological process characterized by massive degeneration and abnormal death of liver cells. With increase in dead cells and necrosis, liver injury eventually leads to nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and even hepatocellular carcinoma (HCC). Consequently, it is necessary to treat liver injury and to prevent its progression. The drug Bicylol is widely employed in China to treat chronic hepatitis B virus (HBV) and has therapeutic potential for liver injury. It is the derivative of dibenzocyclooctadiene lignans extracted from Schisandra chinensis (SC). The Schisandraceae family is a rich source of dibenzocyclooctadiene lignans, which possesses potential liver protective activity. This study aimed to comprehensively summarize the phytochemistry, structure-activity relationship and molecular mechanisms underlying the liver protective activities of dibenzocyclooctadiene lignans from the Schisandraceae family. Here, we had discussed the analysis of absorption or permeation properties of 358 compounds based on Lipinski's rule of five. So far, 358 dibenzocyclooctadiene lignans have been reported, with 37 of them exhibited hepatoprotective effects. The molecular mechanism of the active compounds mainly involves antioxidative stress, anti-inflammation and autophagy through Kelch-like ECH-associating protein 1/nuclear factor erythroid 2 related factor 2/antioxidant response element (Keap1/Nrf2/ARE), nuclear factor kappa B (NF-кB), and transforming growth factor ß (TGF-ß)/Smad 2/3 signaling pathways. This review is expected to provide scientific ideas for future research related to developing and utilizing the dibenzocyclooctadiene lignans from Schisandraceae family.

Mimicking oxidative radical cyclizations of lignan biosynthesis using redox-neutral photocatalysis.

Oxidative cyclizations create many unique chemical structures that are characteristic of biologically active natural products. Many of these reactions are catalysed by 'non-canonical' or 'thwarted' iron oxygenases and appear to involve long-lived radicals. Mimicking these biosynthetic transformations with chemical equivalents has been a long-standing goal of synthetic chemists but the fleeting nature of radicals, particularly under oxidizing conditions, makes this challenging. Here we use redox-neutral photocatalysis to generate radicals that are likely to be involved in the biosynthesis of lignan natural products. We present the total syntheses of highly oxidized dibenzocyclooctadienes, which feature densely fused, polycyclic frameworks that originate from a common radical progenitor. We show that multiple factors control the fate of the proposed biosynthetic radicals, as they select between 5- or 11-membered ring cyclizations and a number of different terminating events. Our syntheses create new opportunities to explore the medicinal properties of these natural products, while shedding light on their biosynthetic origin.

Total Synthesis of the Schisandraceae Nortriterpenoid Rubriflordilactone†A.

Full details of the total synthesis of the Schisandraceae nortriterpenoid natural product rubriflordilactone A are reported. Palladium- and cobalt-catalyzed polycyclizations were employed as key strategies to construct the central pentasubstituted arene from bromoendiyne and triyne precursors. This required the independent assembly of two AB ring aldehydes for combination with a common diyne component. A number of model systems were explored to investigate these two methodologies, and also to establish routes for the installation of the challenging benzopyran and butenolide rings.

Development of a fluorescence-based HIV-1 integrase DNA binding assay for identification of novel HIV-1 integrase inhibitors.

Human immunodeficiency virus integrase (HIV-1 IN) inhibitors that are currently approved or are in advanced clinical trials specifically target the strand transfer step of integration. However, considerable cross-resistance exists among some members of this class of IN inhibitors. Intriguingly, though, HIV-1 IN possesses multiple sites, distinct from those involved in the strand transfer step, that could be targeted to develop new HIV-1 IN inhibitors. We have developed a fluorescent HIV-1 IN DNA binding assay that can identify small molecules termed IN binding inhibitors (INBIs) that inhibit IN binding to viral DNA. This assay has been optimized with respect to concentrations of each protein, long terminal repeat (LTR) DNA substrate, salt, and time, and has been used successfully to measure the HIV-1 IN DNA binding activity of a well-characterized INBI termed FZ41. In addition, we have used the assay to screen a small library of natural products, resulting in the identification of nigranoic acid as a new INBI. The proposed fluorescence assay is easy and inexpensive, and provides a high-throughput detection method for determination of HIV-1 IN DNA binding activity, monitoring of enzyme kinetics, and high-throughput screening for the identification of new INBIs.