An efficient solution phase synthesis of triazadibenzoazulenones: ‘designer isonitrile free’ methodology enabled by microwaves

A novel two-step solution phase protocol for the synthesis of arrays of triazadibenzoazulenones is reported. The methodology employs the Ugi reaction to assemble desired diversity and acid treatment enables two tandem ring closing transformations. The order of ring closure is shown to be key for optimal conversion to the desired tetra-cyclic product and initially proceeds through a benzimidazole intermediate, followed by second ring closure to give the desired fused benzodiazepine. The two-step protocol is further facilitated by microwave irradiation. Prudent selection of the isonitrile reagent enables the correct order of ring forming events. As such the methodology represents the first example of a post-condensation Ugi modification that employs two internal amino nucleophiles.     

A comparison of approaches to estimate the resonance energy

We discuss Ab Initio approaches to calculate the energy lowering (stabilisation) due to aromaticity. We compare the valence bond method and the block-localised wave function approaches to calculate the resonance energy. We conclude that the valence bond approach employs a Pauling–Wheland resonance energy and that the block-localised approach employs a delocalisation criterion. The latter is shown to be more basis set dependent in a series of illustrative calculations.     

A novel strategy for the asymmetric synthesis of chiral cyclopropane carboxaldehydes

A new way of combining chiral auxiliaries and substrate-directable reactions for asymmetric synthesis is described that employs a three-step sequence of aldol-cyclopropanation-retro-aldol reactions for the stereoselective synthesis of enantiopure cyclopropane carboxaldehydes.     

Fully automated sample treatment method for high throughput proteome analysis

The bottom-up strategy for proteome analysis typically employs a multistep sample preparation workflow that suffers from being time-consuming and sample loss or contamination caused by the off-line manual operation.Herein,we developed a hollow fibre membrane(HFM)-aided fully automated sample treatment(FAST)method.Due to the confinement effects of HFMs and the immobilized enzymatic reactor,the proteome samples could be denatured,reduced,desalted and digested within 8–20 min via the one-stop service.This method also showed superiority in trace sample analysis.In one and half hours,we could identify about 1,600 protein groups for 500 HeLa cells as the starting materials,1.5–8 times more than those obtained by previously reported methods.Through the on-line combination of FAST with nano-liquid chromatography-electrospray ionization tandem mass spectrometry(nanoLC-ESI-MS/MS),we further established a fully integrated platform for label-free quantification of proteome with high reproducibility and precision.Collectively,FAST presented here represents a major advance in the high throughput sample treatment and quantitative analysis of proteomes.     

Time-domain zero-field magnetic resonance with field pulse excitation

An improved technique of time-domain zero-field magnetic resonance is proposed which employs a pair of short magnetic field pulses for excitation and detection of free precession.     

Improved Synthesis of Aliphatic Ketones by the Reaction of Alkylmercuric Bromides With Nickel Carbonyl in the Presence of Potassium Iodide

An improved and convenient procedure for symmetrical aliphatic ketone synthesis is described, which employs the reaction of alkylmercuric bromides with nickel carbonyl in the presence of potassium iodide.     

Reactions of alkali metal derivatives of some heterocyclic amines

Procedures are described for converting 2-amino-1,3,4-oxa- and thiadiazoles into various products in one-pot syntheses. The preparative method employs alkali metal derivatives of the heterocyclic amines as the reactive species.     

Photolithographic synthesis of cyclic peptide arrays using a differential deprotection strategy

We report here a strategy for the photolithographic synthesis of diverse, spatially addressable arrays of cyclic peptides which employs a differential deprotection strategy for the combinatorial addition of side chains to a pre-fabricated cyclic core.     

Toward Naphthocyclinones: Doubly Connected Octaketide Dimers with a Bicyclo[3.2.1]octadienone Core by Thiolate‐Mediated Cyclization

A viable method is reported for the synthesis of the bicyclo[3.2.1]octadienone scaffold in naturally occurring octaketide dimers. The procedure employs a reductive cyclization reaction mediated by an unusual ethanedithiol monosodium salt.     

Total Synthesis of (+)‐Dibromophakellin and (+)‐Dibromophakellstatin

A new method for the preparation of quaternary chiral aminals has been developed that employs an enamide‐type Overman rearrangement process. This methodology was applied to enantioselective total syntheses of (+)‐dibromophakellin and (+)‐dibromophakellstatin.     

Phenylsulfenyl chloride/N,N-diisopropylethylamine: A useful reagent for cyclic ether formation (sulfenyletherification)

A general method for the formation of cyclic ethers and lactones is described. The procedure employs phenylsulfenyl chloride and N,N-diisopropylethylamine to generate an episulfonium ion intermediate from which the cyclic products arise by internal nucleophilic displacement.     

Facile fabrication of microfluidic systems using electron beam lithography

We present two fast and generic methods for the fabrication of polymeric microfluidic systems using electron beam lithography: one that employs spatially varying electron-beam energy to expose to different depths a negative electron-beam resist, and another that employs a spatially varying electron-beam dose to differentially expose a bi-layer resist structure. Using these methods, we demonstrate the fabrication of various microfluidic unit structures such as microchannels of a range of geometries and also other more complex structures such as a synthetic gel and a chaotic mixer. These are made without using any separate bonding or sacrificial layer patterning and etching steps. The schemes are inherently simple and scalable, afford high resolution without compromising on speed and allow post CMOS fabrication of microfluidics. We expect them to prove very useful for the rapid prototyping of complete integrated micro/nanofluidic systems with sense and control electronics fabricated by upstream processes.     

Nickel-catalyzed Suzuki-Miyaura reaction of aryl fluorides

Two protocols for the nickel-catalyzed cross-coupling of aryl fluorides with aryl boronic esters have been developed. The first employs metal fluoride cocatalysts, such as ZrF(4) and TiF(4), which enable Suzuki-Miyaura reactions of aryl fluorides bearing electron-withdrawing (ketones, esters, and CF(3)), aryl and alkenyl groups as well as those comprising fused aromatic rings, such as fluoronaphthalenes and fluoroquinolines. The second protocol employs aryl fluorides bearing ortho-directing groups, which facilitate the difficult C-F bond activation process via cyclometalation. N-heterocycles, such as pyridines, quinolines, pyrazoles, and oxazolines, can successfully promote cross-coupling with an array of organoboronic esters. A study into the substituent effects with respect to both coupling components has provided fundamental insights into the mechanism of the nickel-catalyzed cross-coupling of aryl fluorides.     

On the information theoretic prediction of collision probabilities using approximate dynamic constraints

A method which employs quadratic programming is proposed for the information theoretic prediction of collision probabilities, using approximate dynamic constraints. If the original constraints lead to inconsistencies, they are replaced by similar ones which eliminate these inconsistencies.     

Evaluation of thermal stability,an overview

A systematic application of thermal analytical techniques for the assessment of the thermal stability of a material is emphasized. This approach employs ASTM E-27.02 (Methods of Test) and is illustrated using a sulfur—nitrogen heterocyclic compound model.     

First total synthesis of leucamide A

The first total synthesis of marine bioactive cyclic heptapeptide Leucamide A has been accomplished, including a simple method for construction of the 4,2-bisheterocycle tandem pair substructure that employs a DAST-mediated cyclization of beta-hydroxy amide and final HBTU-promoted ring closing.     

Correlating dispersion staining colors to the numerical value of the refractive index for asbestos fibers—an update

An update is presented for the microscopical determination of the refractive index of asbestos, in asbestos containing (bulk) samples, using dispersion staining. The procedure employs the refractive index values published by the National Institute of Standards and Technology (NIST-USA).     

Preparation of silver nanoparticles in solution from a silver salt by laser irradiation

A new method is proposed for the fabrication of a well-defined size and shape distribution of silver nanoparticles in solution; the method employs direct laser irradiation of an aqueous solution containing a silver salt and a surfactant in the absence of reducing agents.     

Gamma-allyl phosphinoyl phenyl sulfone (GAPPS): a conjunctive reagent for the synthesis of EE, EZ, and ET 1,3-dienes

A three-operation conjunctive strategy is available for the synthesis of EE, EZ, and ET dienes. This protocol employs a sequential Wadsworth-Emmons reaction using a GAPPS reagent followed by alkylation of an allylic sulfone anion, and finally ligand-mediated, palladium-catalyzed desulfonylation.