lignans and bursehernin

Topics: Antineoplastic Agents; Caspases; Cell Cycle; Cell Death; Cell Line, Tumor; Humans; Inhibitory Concentration 50; Lactones; Lignans; Models, Biological; Neoplasm Proteins; Neoplasms

Bursehernin (5'-desmethoxyyatein) is a natural lignan, which has anti-tumor activity in vitro. In this study, the binding-inhibitory effects of bursehernin were screening on selected 80 proteins associated with cancer pathway. The computational analysis suggested inhibitory effect due to bursehernin towards proteins related to cancer proliferation, including FMS kinase receptor, heat shock protein 90-α (Hsp90-α), adenylate cyclase 10 (ADCY10), mitogen-activated protein kinase kinase (MEK1), and α-tubulin. Moreover, bursehernin could interfere with cell cycle progression via binding to cyclin B proteins. Among all screened proteins, the compound showed an interesting binding affinity to the FMS kinase receptor. The binding mode studies by molecular dynamic technique showed that aromatic ring of bursehernin compound was responsible for compound-protein interaction through pi-pi stacking with Tyr105 and Phe178 of the FMS kinase receptor. This study suggests that bursehernin has potential for development as an anti-tumor agent with an anti-proliferation, and cell cycle arrest inducing, although further studies are needed.

Topics: Antineoplastic Agents; Binding Sites; Humans; Lactones; Lignans; Molecular Docking Simulation; Molecular Dynamics Simulation; Neoplasm Proteins; Neoplasms; Protein Binding; Protein Conformation, alpha-Helical; Protein Domains; Thermodynamics

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (-)-bursehernin.

Topics: Aldehydes; Alkylation; Biological Products; Catalysis; Lactones; Lignans; Models, Molecular; Oxidation-Reduction; Photochemical Processes; Stereoisomerism

IUPAC defines chemoselectivity as "the preferential reaction of a chemical reagent with one of two or more different functional groups", a definition that describes in rather understated terms the single greatest obstacle to complex molecule synthesis. Indeed, efforts to synthesize natural products often become case studies in the art and science of chemoselective control, a skill that nature has practiced deftly for billions of years but man has yet to master. Confrontation of one or perhaps a collection of functional groups that are either promiscuously reactive or stubbornly inert has the potential to unravel an entire strategic design. One could argue that the degree to which chemists can control chemoselectivity pales in comparison to the state of the art in stereocontrol. In this Account, we hope to illustrate how the combination of necessity and tenacity leads to the invention of chemoselective chemistry for the construction of complex molecules. In our laboratory, a premium is placed upon selecting targets that would be difficult or impossible to synthesize using traditional techniques. The successful total synthesis of such molecules demands a high degree of innovation, which in turn enables the discovery of new reactivity and principles for controlling chemoselectivity. In devising an approach to a difficult target, we choose bond disconnections that primarily maximize skeletal simplification, especially when the proposed chemistry is poorly precedented or completely unknown. By choosing such a strategy--rather than adapting an approach to fit known reactions--innovation and invention become the primary goal of the total synthesis. Delivery of the target molecule in a concise and convergent manner is the natural consequence of such endeavors, and invention becomes a prerequisite for success.

Topics: Alkaloids; Biological Products; Heterocyclic Compounds, 4 or More Rings; Imidazoles; Indole Alkaloids; Indoles; Lactones; Lignans; Neuropeptides; Pyrroles

This full account presents the background on, discovery of, and extensive insight that has been gained into the oxidative intermolecular coupling of two different carbonyl species. Optimization of this process has culminated in reliable and scalable protocols for the union of amides, imides, ketones, and oxindoles using soluble copper(II) or iron(III) salts as oxidants. Extensive mechanistic studies point to a metal-chelated single-electron-transfer process in the case of copper(II), while iron(III)-based couplings appear to proceed through a non-templated heterodimerization. This work presents the most in-depth findings on the mechanism of oxidative enolate coupling to date. The scope of oxidative enolate heterocoupling is extensive (40 examples) and has been shown to be efficient even on a large scale (gram-scale or greater). Finally, the method has been applied to the total synthesis of the unsymmetrical lignan lactone (-)-bursehernin and a medicinally important 2,3-disubstituted succinate derivative.

Topics: Amides; Cations; Chemistry, Organic; Copper; Dimerization; Imides; Indoles; Iron; Ketones; Lactones; Lignans; Models, Chemical; Oxidants; Oxindoles; Salts; Solubility; Stereoisomerism; Succinates

Little is known about the biosynthesis of yatein, in spite of its importance as a typical heartwood lignan and a key biosynthetic intermediate of the antitumor lignan podophyllotoxin. The present study, based on individual administration of [13C]phenylalanine and deuterium labelled lignans and simultaneous administration of two distinct lignans labelled with deuterium atoms to Anthriscus sylvestris, established the two independent branch pathways from matairesinol, one to afford yatein via thujaplicatin, 5-methylthujaplicatin, and 4,5-dimethylthujaplicatin and the other to bursehernin via pluviatolide. The latter pathway did not lead to yatein, eliminating the presence of a metabolic grid from matairesinol to yatein.

Topics: 4-Butyrolactone; Apiaceae; Benzyl Compounds; Carbon Isotopes; Deuterium; Dioxoles; Furans; Lactones; Lignans; Mass Spectrometry; Phenylalanine; Podophyllin

Topics: Benzyl Compounds; Drugs, Chinese Herbal; Lactones; Lignans; Plant Extracts; Plants, Medicinal; Podophyllin; Podophyllotoxin; Seeds