Uncommon reaction in 4-formyl phenols – substitution of the formyl group

4-formyl phenols with electron donating groups in ortho-position react with active alkyl halides in three directions: Williamson reaction up to 48%, aromatic substitution of the formyl group up to 36%, and addition to the ortho-position with dearomatization of the ring up to 10%. The ratio of the products depends on the substituents in the benzene ring and the used alkali and additives

(1S,2S,6S,9S)-6-Methyl-5-oxobicyclo­[4.4.0]decane-2,9-diyl diacetate

The chiral title compound, C15H22O5, is an inter­mediate in the total synthesis of biologically active 9,11-secosterols. In the crystal, the cyclo­hexane rings are trans-fused and both adopt chair conformations. In the crystal, mol­ecules are loosely held together in a layer parallel to (100) by weak inter­molcular C—H⋯O hydrogen bonds accepted by carbonyl O atoms of the acetyl groups

Design and Validation of Novel Chikungunya Virus Protease Inhibitors

Chikungunya virus (CHIKV; genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2. The available three-dimensional (3D) structure of nsP2 protease has made it a target for in silico drug design; however, there is thus far little evidence that the designed compounds indeed inhibit the protease activity of nsP2 and/or suppress CHIKV replication. In this study, a set of 12 compounds, predicted to interact with the active center of nsP2 protease, was designed using target-based modeling. The majority of these compounds were shown to inhibit the ability of nsP2 to process recombinant protein and synthetic peptide substrates. Furthermore, all compounds found to be active in these cell-free assays also suppressed CHIKV replication in cell culture, the 50% effective concentration (EC50) of the most potent inhibitor being similar to 1.5 mu M. Analysis of stereoisomers of one compound revealed that inhibition of both the nsP2 protease activity and CHIKV replication depended on the conformation of the inhibitor. Combining the data obtained from different assays also indicates that some of the analyzed compounds may suppress CHIKV replication using more than one mechanism.Peer reviewe

FRAGMENTATION OF PAMAM DENDRIMERS IN METHANOL

Abstract. The decomposition of ethylenediamine core poly(amidoamine) (PAMAM) dendrimers (generation -0.5) was investigated by gas chromatography. The decomposition of PAMAM dendrimer G-0.5 into triester 2 is caused by the retro-Michael reaction. Equilibrium between the Michael and retro-Michael reactions is shifted towards the retro-Michael reaction at an elevated temperature. Similar decomposition is possible in the case of higher PAMAM dendrimer generations

Metal-Catalyzed Degradation of Cellulose in Ionic Liquid Media

Biomass conversion to 5-hydroxymethylfurfural (HMF) has been widely investigated as a sustainable alternative to petroleum-based feedstock, since it can be efficiently converted to fuel, plastic, polyester, and other industrial chemicals. In this report, the degradation of commercial cellulose, the isomerization of glucose to fructose, and the conversion of glucose to HMF in 1-butyl-3-methylimidazolium chloride ([BMIM]Cl]) using metal catalysts (CrCl3, ZnCl2, MgCl2) as well as tungsten and molybdenum oxide-based polyoxometalates (POM) were investigated. Tungsten and molybdenum oxide-based POMs in ionic liquids (IL) were able to degrade cellulose to majority glucose and epimerize glucose to mannose (in the case of the molybdenum oxide-based POM). A certain amount of glucose was also converted to HMF. The tungsten oxide-based POM in IL showed good activity for cellulose degradation but the overall products yield remained 28.6% lower than those obtained using CrCl3 as a catalyst. Lowering the cellulose loading did not significantly influence the results and the addition of water to the reaction medium decreased the product yields remarkably

Enantioselective One-Pot Synthesis of α,β-Epoxy Ketones via Aerobic Oxidation of Cyclopropanols

An efficient, mild, and environmentally benign method was developed for the asymmetric synthesis of 2-oxyranyl ketones from easily available tertiary cyclopropanols. The one-pot protocol includes the aerobic oxidation of cyclopropanol derivatives catalyzed by Mn­(III) complexes followed by the poly-l-leucine-assisted stereoselective elimination of water from the intermediate peroxides with DBU to afford the corresponding epoxy ketones in high yields and good-to-excellent enantioselectivities (up to 97%)

Remote Activation of the Nucleophilicity of Isatin

The concept of the remote activation of reactivity was first applied in asymmetric organocatalysis. An isatin 3-phenylimine derivative acts as a donor in the thiourea catalyzed asymmetric addition to unsaturated 1,4-ketoesters, affording aza-Michael adducts in high enantiomeric purity and yield

Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via Late- Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin

We present a unified step-economical strategy to access histone deacetylase inhibitory peptides, based on late-stage installation of zinc-binding functionalities via the cleavage of the strained cyclopropane ring in the common pluripotent cyclopropanol precursor. The efficacy of the proposed diversity-oriented approch has been validated by short stereoselective synthesis of a natural product chlamydocin and a number of its analogs.<br /

Electrochemical Hydroxylation of Electron-Rich Arenes in Continuous Flow

Electrochemical hydroxylation of arenes by trifluoroacetic acid provides a straightforward access to aryl oxygen compounds under the mild and environmental benign reaction conditions. Harmful and pollutant stoichiometric amounts of oxidation reagents and the use of metal-catalysts can be avoided. Herein, we present a novel method for the synthesis of hydroxylated products from electron-rich arenes that was achieved by the implementation of a continuous-flow setup. The continuous nature of the process allowed to fine-tune the reactions conditions in order to prevent the decomposition of the sensitive products expanding the reaction scope beyond electron-poor and neutral arenes that were previously reported in the batch processes. Thus, synthetically valuable hydroxylated arenes were obtained in good yields with the residence time just over a minute. In order to demonstrate the reliability and the efficiency of the electrochemical flow setup, a scale up experiment was also performed

Asymmetric Synthesis of Congested Spiro-cyclopentaneoxindoles via an Organocatalytic Cascade Reaction

Starting from simple alkylidene oxindoles and nitroketones, a highly stereoselective methodology was developed for the synthesis of spiro-cyclopentaneoxindoles with four consecutive stereogenic centers. Using an organocatalytic cascade of Michael and aldol reactions in the presence of a chiral thiourea catalyst products were obtained in moderate to high yields and excellent enantioselectivities. Nitro, ester, and hydroxyl groups were introduced to the spiro ring, which could be used to facilitate further functionalization of the products