The [2 + 2] photocycloaddition is undisputedly the most important and most frequently used photochemical reaction. In this review, it is attempted to cover all recent aspects of [2 + 2] photocycloaddition chemistry with an emphasis on synthetically relevant, regio-, and stereoselective reactions. The review aims to comprehensively discuss relevant work, which was done in the field in the last 20 years (i.e., from 1995 to 2015). Organization of the data follows a subdivision according to mechanism and substrate classes. Cu(I) and PET (photoinduced electron transfer) catalysis are treated separately in sections 2 and 4, whereas the vast majority of photocycloaddition reactions which occur by direct excitation or sensitization are divided within section 3 into individual subsections according to the photochemically excited olefin.

http://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.5b00723

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2+2] Photocycloaddition Reactions

Flavonoids and their glycosides, including anthocyanins

The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery Both of these methods have been fruitful However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future Indeed, the number of newly developed antibiotics has decreased dramatically in recent years Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics Traditional medicine plants are likely to provide further new antibiotics in the future However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options Indeed, some combinational antibiotic therapies are already clinically available This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field

/pdf/developing-new-antimicrobial-therapies-are-synergistic-46wiqvtlkm.pdf

Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution?

Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Fibroblast growth factor 21 (FGF21) is a hormone that regulates important metabolic pathways. FGF21 is expressed in several metabolically active organs and interacts with different tissues. The FGF21 function is complicated and well debated due to its different sites of production and actions. Striated muscles are plastic tissues that undergo adaptive changes within their structural and functional properties in order to meet their different stresses, recently, they have been found to be an important source of FGF21. The FGF21 expression and secretion from skeletal muscles happen in both mouse and in humans during their different physiological and pathological conditions, including exercise and mitochondrial dysfunction. In this review, we will discuss the recent findings that identify FG21 as beneficial and/or detrimental cytokine interacting as an autocrine or endocrine in order to modulate cellular function, metabolism, and senescence.

/pdf/fgf21-as-modulator-of-metabolism-in-health-and-disease-33m1kokkz1.pdf

FGF21 as Modulator of Metabolism in Health and Disease.

Novel quinolinone alkaloids bearing a lignoid moiety and related constituents in the leaves of Melicope denhamii

The emergence and spread of multidrug-resistant P. aeruginosa infections is of great concern, as very few agents are effective against strains of this species. Methanolic extracts from the Coptidis Rhizoma (the rhizomes of Coptis japonica var. major Satake) or Phellodendri Cortex (the bark of Phellodendron chinense Schneider) markedly reduced resistance to anti-pseudomonal aminoglycosides (e.g. amikacin) in multidrug-resistant P. aeruginosa strains. Berberine, the most abundant benzylisoquinoline alkaloid in the two extracts, reduced aminoglycoside resistance of P. aeruginosa via a mechanism that required the MexXY multidrug efflux system; berberine also reduced aminoglycoside MICs in Achromobacter xylosoxidans and Burkholderia cepacia, two species that harbor intrinsic multidrug efflux systems very similar to the MexXY. Furthermore this compound inhibited MexXY-dependent antibiotic resistance of other classes including cephalosporins (cefepime), macrolides (erythromycin), and lincosamides (lincomycin) demonstrated using a pseudomonad lacking the 4 other major Mex pumps. Although phenylalanine-arginine beta-naphthylamide (PAβN), a well-known efflux inhibitor, antagonized aminoglycoside in a MexXY-dependent manner, a lower concentration of berberine was sufficient to reduce amikacin resistance of P. aeruginosa in the presence of PAβN. Moreover, berberine enhanced the synergistic effects of amikacin and piperacillin (and vice versa) in multidrug-resistant P. aeruginosa strains. Thus, berberine appears to be a novel type inhibitor of the MexXY-dependent aminoglycoside efflux in P. aeruginosa. As aminoglycosides are molecules of choice to treat severe infections the clinical impact is potentially important.

/pdf/berberine-is-a-novel-type-efflux-inhibitor-which-attenuates-4y5h5hiewr.pdf

Berberine Is a Novel Type Efflux Inhibitor Which Attenuates the MexXY-Mediated Aminoglycoside Resistance in Pseudomonas aeruginosa.

The three novel methylene bis[flavonoids] 1–3, the novel 2-flavene 4, the new naturally occurring flavan 5, and the new retro-dihydrochalcone 6 were isolated from dragon's blood of Daemonorops draco, together with seven known compounds. The structures were elucidated by extensive 1D- and 2D-NMR spectroscopic analysis.

Novel Flavonoids in Dragon's Blood of Daemonorops draco

Brazilian green propolis is produced by mixing secretions from Africanized honey bees with exudate, mainly from Baccharis dracunculifolia. Brazilian propolis is especially rich in flavonoids and cinammic acid derivatives, and it has been widely used in folk medicine owing to its anti-inflammatory, anti-viral, tumoricidal, and analgesic effects. Moreover, it is applied to prevent metabolic disorders, such as type 2 diabetes and arteriosclerosis. Previously, we demonstrated that propolis ethanol extract ameliorated type 2 diabetes in a mouse model through the resolution of adipose tissue inflammation. The aims of this study were to identify the immunosuppressive cells directly elicited by propolis extract and to evaluate the flavonoids that induce such cells. Ethanol extract of Brazilian propolis (PEE; 100 mg/kg i.p., twice a week) was injected into lean or high fat-fed obese C57BL/6 mice or C57BL/6 ob/ob mice for one month. Subsequently, immune cells in visceral adipose tissue and the peritoneal cavity were monitored using FACS analysis. Isolated macrophages and the macrophage-like cell line J774.1 were treated with PEE and its constituent components, and the expression of immune suppressive myeloid markers were evaluated. Finally, we injected one of the identified compounds, kaempferol, into C57BL/6 mice and performed FACS analysis on the adipose tissue. Intraperitoneal treatment of PEE induces CD11b+, Gr-1+ myeloid-derived suppressor cells (MDSCs) in visceral adipose tissue and the peritoneal cavity of lean and obese mice. PEE directly stimulates cultured M1 macrophages to transdifferentiate into MDSCs. Among twelve compounds isolated from PEE, kaempferol has an exclusive effect on MDSCs induction in vitro. Accordingly, intraperitoneal injection of kaempferol causes accumulation of MDSCs in the visceral adipose tissue of mice. Brazilian PEE and its compound kaempferol strongly induce MDSCs in visceral adipose tissue at a relatively early phase of inflammation. Given the strong anti-inflammatory action of MDSCs, the induction of MDSCs by PEE and kaempferol is expected to be useful for anti-diabetic and anti-inflammatory therapies.

/pdf/brazilian-propolis-ethanol-extract-and-its-component-tjhtmcnuie.pdf

Ken-ichi Nakashima

Papers

Novel quinolinone alkaloids bearing a lignoid moiety and related constituents in the leaves of Melicope denhamii

Berberine Is a Novel Type Efflux Inhibitor Which Attenuates the MexXY-Mediated Aminoglycoside Resistance in Pseudomonas aeruginosa.

Novel Flavonoids in Dragon's Blood of Daemonorops draco

Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro

Melicodenines A and B, novel Diels–Alder type adducts isolated from Melicope denhamii