PubMed Journal Database | Organic & biomolecular chemistry

Glutathione and thioredoxin type 1 cooperatively denitrosate HepG2 cells-derived cytosolic S-nitrosoproteins.

In this study, we present experimental evidence that glutathione acts in concert with human thioredoxin type 1 in the denitrosation of cytosolic S-nitrosoproteins (PSNOs) from HepG2 cells.

Manganese-catalyzed aerobic dehydrogenative cyclization toward ring-fused indole skeletons.

We describe the first example of manganese(iii)-catalyzed aerobic dehydrogenative cyclization producing ring-fused indole skeletons. This catalytic system converts from two C-H bonds of indole and malonate to a C-C bond and produces water as the sole side product. This operationally easy method was extended to an intermolecular cross-dehydrogenative coupling of indole and α-substituted malonate with complete C2-selectivity.

AApeptides as a new class of antimicrobial agents.

Antibiotic resistance is an increasing public health concern around the world, and is recognized as one of the greatest threats facing humankind in the 21(st) century. Natural antimicrobial peptides (AMPs) are small cationic amphiphilic peptides found in virtually all living organisms, and play a key role in the defense against bacterial infections. Compared with conventional antibiotics, which target specific metabolic processes, AMPs are able to adopt globally amphipathic conformations, and kill bacteria...

Enantioselective Mukaiyama-Michael with 2-enoyl pyridine N-oxides catalyzed by PYBOX-DIPH-Zn(ii)-complexes at ambient temperature.

A chiral PYBOX-DIPH-Zn(ii) catalyzed enantioselective Mukaiyama-Michael reaction of acyclic silyl enol ethers with 2-enoylpyridine N-oxides has been studied in external additive free conditions at ambient temperature. The methodology offers straightforward access to a variety of functionalized chiral 1,5-dicarbonyl compounds, which could easily be elaborated into synthetically viable pyrones via hydrolysis followed by cyclization. A transition state model has been proposed to explain the stereochemical outc...

Chemical approach for interconversion of (S)- and (R)-α-amino acids.

Here we report a general method for the preparation of unnatural (R)-α-amino acids via complexation of α-(phenyl)ethylamine derived chiral reagent (S)- with various (S)-α-amino acids. The reactions proceed with synthetically useful chemical yields and thermodynamically controlled diastereoselectivity. Chiral reagent (S)- can be conveniently recovered and reused without any loss of enantiomeric purity and reactivity.

Ligand and substrate effects during Pd-catalyzed cyclizations of alkyne-tethered cyclohexadienones.

The effects of ligand and substrate choice on the Pd-catalyzed cyclization of alkyne-tethered cyclohexadienones were examined. In the presence of a chiral ligand, the enantioselectivity of the desymmetrization is remarkably sensitive to structural changes in both the ligand and the substrate. Additionally, the regioselectivity of the reaction (5- vs. 6-membered ring formation) is dependent on the proximity of heteroatoms to the alkyne.

Tunable peptoid microspheres: effects of side chain chemistry and sequence.

Peptoids are a versatile family of oligomeric synthetic molecules that can be customized for many applications. The submonomer solid-phase synthesis of peptoids allows for quick and inexpensive manufacturing and the selection of side chains is nearly limitless. In addition, peptoids that include chiral, aromatic side chains form stable helical secondary structure that leads to the potential for the formation of supramolecular assemblies. The effects of water solubility, helical content, charge placement, an...

Synthesis of bis-α,α'-amino acids through diastereoselective bis-alkylations of chiral Ni(ii)-complexes of glycine.

The Ni(ii) complex derived from glycine Schiff base with (S)-N-(benzylprolyl)-2-aminobenzophenone can be effectively alkylated with α,ω-dibromide reagents to furnish the corresponding bis-alkylated products. This method presents a direct approach for the preparation of the corresponding bis-α,α'-amino acids with high biological importance. Heterogeneous (phase-transfer) as well as homogeneous conditions for the alkylation reactions have been investigated and the latter proved to be more efficient in ter...

Chemoselective fragment condensation between peptide and peptidomimetic oligomers.

We report the first example of chemoselective fragment condensation, through native amide bond formation, between peptoid and peptide oligomers. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to peptides containing N-terminal serine or threonine residues. We investigate the ligation efficiency of peptoid oligomers varying in length, sequence, and C-terminal steric bulk. These protocols enhance accessibility of structurally complex peptoid-peptide hybrids and will fa...

Discovery of new heterocycles with activity against human neutrophile elastase based on a boron promoted one-pot assembly reaction.

Herein we demonstrate for the first time that a boron promoted one-pot assembly reaction may be used to discover novel enzyme inhibitors. Inhibitors for HNE were simply assembled in excellent yields, high diastereoselectivities and IC50 up to 1.10 μM, based on components like salicylaldehyde, aryl boronic acids and amino acids. The combination of synthetic, biochemical, analytical and theoretical studies allowed the identification of the 4-methoxy or the 4-diethyl amino substituent of the salicylaldehyde a...

Optimising the synthesis, polymer membrane encapsulation and photoreduction performance of Ru(ii)- and Ir(iii)-bis(terpyridine) cytochrome c bioconjugates.

Ruthenium(ii) and iridium(iii) bis(terpyridine) complexes were prepared with maleimide functionalities in order to site-specifically modify yeast iso-1 cytochrome c possessing a single cysteine residue available for modification (CYS102). Single X-ray crystal structures were solved for aniline and maleimide Ru(ii) and Ru(ii) , respectively, providing detailed structural detail of the complexes. Light-activated bioconjugates prepared from Ru(ii) in the presence of tris(2-carboxyethyl)-phosphine (TCEP) signif...

DiGalactosyl-Glycero-Ether Lipid: synthetic approaches and evaluation as SK3 channel inhibitor.

The recent discoveries of the involvement of SK3 channel in some cell motility mechanisms occurring in cancer disease have opened up the way to the synthesis of inhibitors that could reduce metastasis formation. On the basis of our recent previous works showing that both lactose-glycero-ether lipid () and some phosphate analogues () were efficient compounds to modulate SK3 channel activity, the present study, which found its inspiration in the structure of the natural glycolipid DiGalactosylDiacylGlycerol (...

The phenacyl group as an efficient thiol protecting group in a peptide condensation reaction by the thioester method.

One of the condensation methods for the preparation of long-chain peptides, the so-called thioester method requires protecting groups for amino and thiol groups for regioselective ligation. In this study, we demonstrated that the phenacyl (Pac) group acts as an efficient protecting group of cysteine side chains. We synthesized a cysteine derivative carrying the Pac group at the side chain sulfur atom, and Pac-containing peptides and peptide thioesters were synthesized using it by the ordinary 9-fluorenylmet...

Convenient in situ generation of various dichlorinating agents from oxone and chloride: diastereoselective dichlorination of allylic and homoallylic alcohol derivatives.

A safe and convenient protocol was developed for in situ generation of various dichlorinating agents (cf. Cl2, NCl3, Et4NCl3, ArICl2) from oxone and chloride. The synthetic utility of this protocol was demonstrated by diastereoselective dichlorination of a series of allylic and homoallylic alcohol derivatives with excellent yields and diastereoselectivity.

CLIP-HSQMBC: easy measurement of small proton-carbon coupling constants in organic molecules.

A user-friendly 2D NMR approach denoted as CLIP-HSQMBC is proposed for the very easy, direct and accurate measurement of long-range proton-carbon coupling constants in organic molecules and natural products. The J value can be extracted directly from the analysis of resolved in-phase (1)H multiplets that show an additional splitting arising from the proton-carbon coupling. In cases of unresolved peaks, a simple fitting analysis using the internal satellite lines as a reference is performed. Addition of a sp...

Bu4NI-catalyzed decarboxylative acyloxylation of an sp(3) C-H bond adjacent to a heteroatom with α-oxocarboxylic acids.

A novel metal-free decarboxylative acyloxylation of an sp(3) C-H bond in formamides and ethers has been explored. A variety of N-acyloxymethylamides and α-acyloxy ethers could be easily synthesized by this method. Preliminary mechanistic studies have shown that the reaction proceeded via a radical process.

Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria.

JP4-039 is a lead structure in a series of nitroxide conjugates that are capable of accumulating in mitochondria and scavenging reactive oxygen species (ROS). To explore structure-activity relationships (SAR), new analogs with variable nitroxide moieties were prepared. Furthermore, fluorophore-tagged analogs were synthesized and provided the opportunity for visualization in mitochondria. All analogs were tested for radioprotective and radiomitigative effects in 32Dcl3 cells.

Aerobic C-H amination of tetrahydrocarbazole derivatives via photochemically generated hydroperoxides.

A Brønsted acid catalyzed C-H functionalization via Intermediate PeroxideS (CHIPS), generated photochemically, allows the oxidative coupling of indole derivatives with a variety of nitrogen nucleophiles. The reaction can be performed in one pot and requires only visible light, elemental oxygen, a Brønsted acid and a photosensitizer. The method can be applied to an efficient synthesis of some biologically active compounds.

Platinum catalysed hydrosilylation of propargylic alcohols.

A facile and user-friendly protocol has been developed for the selective synthesis of E-vinyl silanes derived from propargylic alcohols using a PtCl2/XPhos catalyst system. The reaction is generally high yielding and provides a single regioisomer at the β-position with E-alkene geometry. The reaction is extremely tolerant of functionality and has a wide scope of reactivity both in terms of alkynes and silanes used. The catalyst loading has been investigated and it is found that good reactivity is observed...

Hybrid photoactive fullerene derivative-ruboxyl nanostructures for photodynamic therapy.

Here we report the investigation of photophysical properties and photodynamic action of two novel water soluble hybrid molecular structures based on [60]fullerene dyads bearing covalently attached residues of anthracycline antibiotic "ruboxyl". Molecular structures of the designed compounds were confirmed by IR and UV-VIS absorption spectroscopy, electrospray mass spectrometry (compound ), and (1)H and (13)C NMR spectroscopy. Dynamic light scattering, steady-state and kinetic fluorimetry and UV-VIS absorpti...

The heterocyclic ring of 4-substituted-1,8-naphthalimides is NOT inert to nucleophilic attack, contrary to earlier reports.

The heterocyclic ring of N-aryl-4-chloro-1,8-naphthalimides, reported to be resistant to nucleophilic attack, reacts with primary amine nucleophiles at room temperature to give 4-chloro-N-alkyl-1,8-naphthalimides. The reaction is first order in the naphthalimide. The Hammett plot is linear (R(2) 0.996) with a large positive slope (+3.0), consistent with substantial negative charge development at nitrogen in the activated complex.

Aniline mediated oxidative C-C bond cleavage of α-alkoxy aldehydes in air and a model reaction for the synthesis of α-(d)-amino acid derivatives.

A metal-free and 4-methyl aniline mediated method for the oxidative C-C bond cleavage has been developed. The reaction proceeds in air using molecular oxygen as the oxidant, affording one-carbon shortened esters in moderate to good yields within a short time. Moreover, it provides a model reaction for the highly enantioselective synthesis of (d)-serine esters by combining with a l-proline catalyzed Mannich reaction.

Multiple-input and visible-output logic gates using signal-converting DNA machines and gold nanoparticle aggregation.

We report a facile design method for constructing multiple-input and visible-output logic gates by combining signal-converting DNA machines and the gold nanoparticle aggregation-based foundational AND gate.

"Dba-free" palladium intermediates of the Heck-Matsuda reaction.

The "dba-free" Heck-Matsuda reaction was investigated via direct ESI-MS(/MS) monitoring. Palladium species involved in the reduction of Pd(ii) during a Wacker type reaction and several "dba-free" arylpalladium transient complexes were detected and characterized. Based on these findings, a more comprehensible catalytic cycle for this pivotal reaction is suggested.

Diversity-oriented synthesis of pyrazolo4,3-bindoles by gold-catalysed three-component annulation: application to the development of a new class of CK2 inhibitors.

Pyrazolo[4,3-b]indole derivatives have been designed as novel CK2 inhibitor compounds based on the binding mode analysis of a previously reported phenylpyrazole-type CK2 inhibitor. A series of pyrazolo[4,3-b]indoles and related dihydropyrazolo[4,3-b]indoles were efficiently prepared from simple starting materials using a gold-catalysed three-component annulation reaction as a key step. Several of the newly synthesized compounds displayed high levels of inhibitory activity, indicating that the pyrazolo[4,3-b...