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A facile synthesis of the 4-aza-analogs of 1-arylnaphthalene lignans chinensin, justicidin B, and Taiwanin C

Reaction of anilines 1a-d with retronic acid (2) or 1,3- cyclopentanedione (3) produced anilinolactones 4a-d and anilinocyclopentenone 5a, respectively, which were then condensed with benzaldehydes to yield 4- aza-1-arylnaphthalene lignan analogs 6-19.

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Microwave-assisted Claisen rearrangement on a silica gel support

A fast, efficient and environmentally benign solvent-free procedure has been developed for microwave-assisted Claisen rearrangement on a silica gel support. A fast, efficient and environmentally benign solvent-free procedure has been developed for microwave-assisted Claisen rearrangement on a silica gel support. Various bis-allyl ketones were prepared using this protocol.

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Bioactive marine sesterterpenoids

Terpenoids are by far the largest class of natural products. Within this class of compounds, the sesterterpenes form a rare group of isoprenoids, which occur in widely differing source. Marine organisms have provided a large number of sesterterpenoids, possessing novel carbon skeleton and a wide variety of biological activities. The more significant sesterterpenoids from marine organisms, which show biological activities, are reported and they are grouped in a biogenetic sequence. Natural products that do not contain 25 carbon atoms but are obviously sesterterpene derivatives are also included. The anti-inflammatory activity is the most relevant among the biological activities observed for marine sesterterpenoids. The high potential for some of these products suggested that they could be developed as drugs for the treatment of inflammation. The different directions that can be taken to obtain quantities of secondary metabolites are reported.

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3-Acylated tetramic and tetronic acids as natural metal binders: Myth or reality?

Covering: up to 2015 3-Acylated tetramic and tetronic acids are characterized by a low pKa and are likely to be deprotonated under physiological conditions. In addition, their structure makes them excellent chelators of metallic cations. We will discuss the significance of these chemical properties with regard to the biological properties and mechanisms of action of these compounds, highlighting the importance of considering them as salts or chelates for biological purposes, rather than acids.

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Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells

Class III beta-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton, GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1 interaction could potentially revert resistance to paclitaxel. A panel of 44 4-azapodophyllotoxin derivatives was screened in the NCI-60 cell panel. The result is that 31 are active and the comparative analysis demonstrated specific activity in paclitaxel-resistant cells. Using surface plasmon resonance, we were able to prove that NSC756093 is a potent in vitro inhibitor of the GBP1:PIM1 interaction and that this property is maintained in vivo in ovarian cancer cells resistant to paclitaxel. Through bioinformatics, molecular modeling, and mutagenesis studies, we identified the putative NSC756093 binding site at the interface between the helical and the LG domain of GBP1. According to our results by binding to this site, the NSC756093 compound is able to stabilize a conformation of GBP1 not suitable for binding to PIM1.

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Recent advances in the development of ubiquitin-specific-processing protease 7 (USP7) inhibitors

Ubiquitin-specific-processing protease 7 (USP7) is one among the several deubiquitinating enzymes gaining central attention in the current cancer research. Most recent studies have focused on illustrating how USP7 is involved in the cancer process, while few articles reported the development of small molecule USP7 inhibitors. Although some review articles dealt with USP7, they mainly focused on its physiological role and not on the development of USP7 inhibitors. In this review, we systematically summarise the structures, activities and structure-activity relationship (SAR) of small molecule USP7 inhibitors, recently disclosed in scientific articles and patents from 2000 to 2019. The binding modes of typical compounds and their interactions with USP7 are also presented, while other deubiquitinase inhibitors are described in detail. Meanwhile, we briefly introduce the biochemical and physiological functions of USP7. Finally, challenges and potential strategies in developing small molecule USP7 inhibitors are also discussed.

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A simple resolution of 4-bromo-2-(tert-butyldimethylsiloxy)furan from tetrahydro-2,4-dioxofuran

A convenient procedure for the synthesis of 4-bromo-2,5-dihydro-2-oxofuran (4) from tetrahydro-2,4-dioxofuran (3) by reaction with a Vilsmeier reagent prepared from oxalyl bromide and dimethylformamide is given. Compound 3 reacts with tert-butyldimethylsilyl trifluoromethanesulfonate to 4-bromo-2-(tert-butyldimethylsiloxy)furan (5c), a stable synthetic precursor for 2,5-dihydro-2-oxofuranide (1).

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Physicochemical characterization of Theobroma cacao L. sweatings in Ecuadorian coast

In 2014, Ecuador generated 141,000 MT of cocoa sweatings equivalent to 12,320 MT of reducing sugars that through fermentation can become Bioetanol. Cocoa sweatings was characterized to determinate its potential as biofuel. Methodologies described by AOAC 2005 standards were used. Values of 10.6 Brix; pH 3.58; density 1.10 g/ml, total sugars 12,33% reducing sugars 6.39% were observed. Chemical groups such as alkaloids, reducing sugars, and coumarins triterpenoid were identified by phytochemical screeninng. 20 chemical compounds were detected using by gas chromatography mass spectrometry (GC-MS): 3 carboxilic acids, 4 sugar acids, 3 sugar alcohols, 2 amino acids, 1 furan, 2 lactones, 1 monosaccharides, 2 disaccharides and 2 glycosides. They represent the 11.08% of total compounds separated, and Sucrose (2.15%), glucose (2.13%) and fructose (4.42%) were identified by high performance liquid chromatography (HPLC). The study showed that for each kilogram of dry cocoa produced 0.59 kg of mucilage are obtained and its sugars are an interesting source of raw material for the production of second generation bioethanol, results that contribute to reducing the environmental impact that generate these waste.

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Selective iron-catalyzed cross-coupling reactions of Grignard reagents with enol triflates, acid chlorides, and dichloroarenes

Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)3 are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C-C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron-ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)2]n generated in situ. Control experiments using the ate-complex [Me4Fe]Li2 corroborate this interpretation.

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Conformationally restricted beta-amino acid isosteres prepared through regioselectively controlled aza-annulation’

A variety of electron withdrawing substituents were used to enhance the aza-annulation of enamines with acryloyl chloride, to direct the regioselectivity of alkene formation, and to facilitate hydrogenation of the unsaturated annulation product. The resulting delta-lactam products were beta-amino acid analogs with structural features similar to those of established peptide isosteres.

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