Sparse canonical correlation analysis applied to ‐omics studies for integrative analysis and biomarker discovery

With the rapid development of new ‐omics measurement methods, there is an increasing interest in studying the correlation structure between two or more data sets. Multivariate methods such as canonical correlation analysis (CCA) have been proposed to analyze the intrinsic correlation relationship by integrating two data sets. However, because of the high dimensionality of data and the relative scarcity of samples, the ordinary CCA is usually faced with variable selection problems and thereby fails to obtain a satisfactory relationship. Here, we explored the potential of sparse CCA (SCCA) to find the correlative components in two sparse views. SCCA aims at finding sparse projection directions to well extract the correlation between two data sets. We applied this method to one simulation data and one real ‐omics data to illustrate the performance of SCCA. The results from two studies show that SCCA could effectively find the correlated patterns between two data sets, which are of high importance for understanding the relationship between two underlying chemical or biological processes. The corresponding variable subsets selected by sparse weight vectors can assist in a better interpretation of the chemical or biological process. The integrative analysis from two views by SCCA helps in improving the discriminative ability of classification models for various ‐omics studies. Copyright © 2015 John Wiley & Sons, Ltd.     

High‐abundance protein depletion: Comparison of methods for human plasma biomarker discovery

Affinity depletion of abundant proteins from human plasma has become a routine sample preparation strategy in proteomics used prior to protein identification and quantitation. To date, there have been limited published studies comparing the performance of commercially available depletion products. We conducted a thorough evaluation of six depletion columns using 2‐DE combined with sophisticated image analysis software, examining the following criteria: (i) efficiency of high‐abundance protein depletion, (ii) non‐specific removal of other than the targeted proteins and (iii) total number of protein spots detected on the gels following depletion. From all the products investigated, the Seppro IgY system provided the best results. It displayed the greatest number of protein spots on the depleted plasma gels, minimal non‐specific binding and high efficiency of abundant protein removal. Nevertheless, the increase in the number of detected spots compared with the second best performing and cheaper multiple affinity removal column (MARC) was not shown to be statistically significant. The ProteoPrep spin column, considered to be the “deepest” depletion technique available at the time of conducting the study, surprisingly displayed significantly fewer spots on the flow‐through fraction gels compared with both the Seppro and the MARC. The spin column format and low plasma capacity were also found to be impractical for 2‐DE. To conclude, we succeeded in providing an overview of the depletion columns performances with regard to the three examined areas. Our study will serve as a reference to other scientists when deciding on the optimal product for their particular projects.     

2,5‐Bis(2‐(diphenylphosphino)phenyl)‐1,3,4‐oxadiazole ligands and their Cu(I) complexes for Sonogashira coupling reaction

Two diphosphane ligands – 2,5‐bis(2‐(diphenylphosphino)‐5‐R)phenyl)‐1,3,4‐oxadiazole ( L1 , R = H, L2 , R = OMe) and their binuclear complexes, L1Cu and L2Cu , were prepared and characterized. The molecular structures of L1Cu and L2Cu , as perchlorate salts, were established by X‐ray crystallography, which showed them to be binuclear complexes with each Cu atom tetrahedrally coordinated by two P atoms and two N atoms. The ligands and their Cu(I) complexes catalyzed Sonogashira coupling reactions of iodobenzene with phenylacetylene in the presence of K₂CO₃ under Pd‐free conditions. Coupling reactions catalyzed by L1 or L2 with Cu(MeCN)₄ClO₄ in situ exhibited better yields than those by the corresponding Cu(I) complexes L1Cu or L2Cu . Detailed studies showed L1 or L2 with Cu(MeCN)₄ClO₄ to be suitable catalysts for the coupling reaction of terminal alkynes and aryl halides. The coupling reactions of aryl iodides with electron‐withdrawing groups showed better results. Copyright © 2014 John Wiley & Sons, Ltd.     

The reaction of (N‐isocyanimino) triphenylphosphorane with (E)‐3‐aryl‐2‐ propenoic acid derivatives: One‐pot synthesis of 2‐[(E)‐2‐aryl‐1‐ethenyl]‐1,3,4‐oxadiazoles via intramolecular aza‐Wittig reaction

The reaction of (E)‐3‐aryl‐2‐propenoic acid derivatives with (N‐isocyanimino) triphenylphosphorane proceeds smoothly at room temperature to afford the corresponding 2‐[(E)‐2‐aryl‐1‐ethenyl]‐1,3,4‐oxadiazole via an intramolecular aza‐Wittig reaction in good yields under neutral conditions. The structures of the products were deduced from their IR, ¹H NMR, and ¹³C NMR spectra and mass spectrometry. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:612–616, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20701     

Metabolic profiling study on potential toxicity and immunotoxicity‐biomarker discovery in rats treated with cyclophosphamide using HPLC‐ESI‐IT‐TOF‐MS

Despite the recent advances in understanding toxicity mechanism of cyclophosphamide (CTX), the development of biomarkers is still essential. CTX‐induced immunotoxicity in rats by a metabonomics approach was investigated using high‐performance liquid chromatography coupled with ion trap time‐of‐flight mass spectrometry (HPLC‐ESI‐IT‐TOF‐MS). The rats were orally administered CTX (30 mg/kg/day) for five consecutive days, and on the fifth day samples of urine, thymus and spleen were collected and analyzed. A significant difference in metabolic profiling was observed between the CTX‐treated group and the control group by partial least squares‐discriminant analysis (PLS‐DA), which indicated that metabolic disturbances of immunotoxicity in CTX‐treated rats had occurred. One potential biomarker in spleen, three in urine and three in thymus were identified. It is suggested that the CTX‐toxicity mechanism may involve the modulation of tryptophan metabolism, phospholipid metabolism and energy metabolism. This research can help to elucidate the CTX‐influenced pathways at a low dose and can further help to indicate the patients' pathological status at earlier stages of toxicological progression after drug administration. Copyright © 2014 John Wiley & Sons, Ltd.     

Darzens reaction of 2‐bromo‐4,6‐dimethoxy‐3(2H)‐benzofuranone with aromatic aldehydes to form flavonoids

The applicability of 2‐bromo‐4,6‐dimethoxy‐3(2H)‐benzofuranone ( 1 ) to produce flavonoid‐derived epoxides in the course of the Darzens reaction with aldehydes was investigated. However, instead of the epoxides, flavonols 3 and, in certain cases, benzofuranyl‐substituted flavonols 4 were isolated. The generation of 3 is assumed due to a ring expansion of the initially formed epoxides. These flavonols can react with 1 to produce the unexpected 1:2 adducts 4 as minor products. The structure of the hexamethoxy derivative 4b (R¹ = H, R² = R³ = OMe) was confirmed by X‐ray crystallographic analysis.     

Kinetic study of the Ce(III)‐, Mn(II)‐ or Fe(phen)32+‐catalyzed Belousov‐Zhabotinsky reaction with 2‐ketoglutaric acid

The Belousov‐Zhabotinsky (BZ) reaction of bromate ion with 2‐ketoglutaric acid (KGA) in aqueous sulfuric acid catalyzed by Ce(III), Mn(II), or Fe(phen)₃²⁺ ion exhibits sustained barely damped oscillations under aerobic conditions. In general, the reaction oscillates without an induction period. Fe(phen)₃²⁺ ion behaves differently from Ce(III) and Mn(II) ions in catalyzing this oscillating system. The gem‐diol form of KGA exhibits different behavior from that of the keto form of KGA in the BZ reaction. The kinetics and mechanism of the reaction of KGA with Ce(IV), Mn(III), or Fe(phen)₃³⁺ ion was investigated. The order of relative reactivities of metal ions toward reaction with KGA is Mn(III) > Ce(IV) ≫ Fe(phen)₃³⁺. Experimental results are rationalized. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 101–107, 2001     

(S)‐3‐(Ammoniomethyl)‐5‐methylhexanoate (pregabalin)

The title compound, C₈H₁₇NO₂, exists as a zwitterion, adopting a propeller conformation. Molecules self‐assemble to form a hydrogen‐bonded layer parallel to the ab crystallographic plane connected by N⁺—H...O⁻ and C—H...O⁻ hydrogen bonds. These layers are stacked along the c axis and are stabilized by van der Waals interactions.     

(R)‐4‐(4‐Aminophenyl)‐2,2,4‐trimethylchroman and (S)‐4‐(4‐aminophenyl)‐2,2,4‐trimethylthiachroman

The title compounds, C₁₈H₂₁NO and C₁₈H₂₁NS, in their enantiomerically pure forms are isostructural with the enantiomerically pure 4‐(4‐hydroxyphenyl)‐2,2,4‐trimethylchroman and 4‐(2,4‐dihydroxyphenyl)‐2,2,4‐trimethylchroman analogues and form extended linear chains via N—H...O or N—H...S hydrogen bonding along the [100] direction. The absolute configuration for both compounds was determined by anomalous dispersion methods with reference to both the Flack parameter and, for the light‐atom compound, Bayesian statistics on Bijvoet differences.     

H‐transfer reaction during decomposition of N‐(2‐methylpropyl)‐ N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐N‐oxyl (SG1)‐based alkoxyamines

Thermal decomposition of four tertiary N‐(2‐methylpropyl)‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐N‐oxyl (SG1)‐based alkoxyamines (SG1‐C(Me)₂‐C(O)‐OR, R = Me, tBu, Et, H) has been studied at different experimental conditions using ¹H and ³¹P NMR spectroscopies. This experiment represents the initiating step of methyl methacrylate polymerization. It has been shown that H‐transfer reaction occurs during the decomposition of three alkoxyamines in highly degassed solution, whereas no products of H‐transfer are detected during decomposition of SG1‐MAMA alkoxyamine. The value of the rate constant of H‐transfer for alkoxyamines 1 (SG1‐C(Me)₂‐C(O)‐OMe) and 2 ( SG1‐C(Me)₂‐C(O)‐OtBu) has been estimated as 1.7 × 10³ M^?1s^?1. The high influence of oxygen on decomposition mechanism is found. In particular, in poorly degassed solutions, nearly quantitative formation of oxidation product has been observed, whereas at residual pressure of 10^?5 mbar, the main products originate from H‐atom transfer reaction. The acidity of the reaction medium affects the decomposition mechanism suppressing the H‐atom transfer. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

A one‐pot efficient four‐component reaction for the synthesis of 2‐(arylamino)‐2‐(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)propyl benzoate (or acetate) derivatives

Reactions of (N‐isocyanimino) triphenylphosphorane with 2‐oxopropylbenzoate (or acetate) in the presence of aromatic carboxylic acids and primary amines proceed smoothly at room temperature and in neutral conditions to afford sterically congested 1,3,4‐oxadiazole derivatives in high yields. The reaction proceeds smoothly and cleanly under mild conditions, and no side reactions were observed. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:692–698, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20735     

A highly efficient synthesis of (Z)‐1‐aryl‐2‐silyl‐1‐ stannylethenes and their conversion to (E)‐2‐ arylethenyl‐, (Z)‐2‐(2‐pyridyl)ethenyl‐ and allenyl‐silanes

A Pd(dba)₂–P(OEt)₃ combination allowed the silastannation of arylacetylenes, 1‐hexyne or propargyl alcohols with tributyl(trimethylsilyl)stannane to take place at room temperature, producing (Z)‐2‐silyl‐1‐stannyl‐1‐substituted ethenes in high yields. Novel silyl(stannyl)ethenes were fully characterized by ¹H‐, ¹³C‐, ²⁹Si‐ and ¹¹⁹Sn‐NMR as well as infrared and mass analyses. Treatment of a series of (Z)‐1‐aryl‐2‐silyl‐1‐stannylethenes and (Z)‐1‐(3‐pyridyl)‐2‐silyl‐1‐stannylethene with hydrochloric acid or hydroiodic acid in the presence of tetraethylammonium chloride (TEACl) or tetrabutylammonium iodide (TBAI) led to the exclusive formation of (E)‐trimethyl(2‐arylethenyl)silanes with high stereoselectivity. A similar reaction of (Z)‐1‐(2‐anisyl)‐2‐silyl‐1‐stannylethene also produced E‐type trimethyl[2‐(2‐anisyl)ethenyl]silane, while (Z)‐trimethyl [2‐(2‐pyridyl)ethenyl]silane was produced exclusively from (Z)‐1‐(2‐pyridyl)‐2‐silyl‐1‐stannylethene. Protodestannylation of (Z)‐1‐[hydroxy(phenyl)methyl]‐2‐silyl‐1‐stannylethene with trifluoroacetic acid took place via the β‐elimination of hydroxystannane, providing trimethyl(3‐phenylpropa‐1,2‐dienyl)silane quite easily. The destannylation products were also fully characterized. Copyright © 2007 John Wiley & Sons, Ltd.     

(E)‐N′‐(4‐Chlorobenzylidene)‐, (E)‐N′‐(4‐bromobenzylidene)‐ and (E)‐N′‐[4‐(diethylamino)benzylidene]‐ derivatives of 4‐hydroxybenzohydrazide

The 4‐chloro‐ [C₁₄H₁₁ClN₂O₂, (I)], 4‐bromo‐ [C₁₄H₁₀BrN₂O₂, (II)] and 4‐diethylamino‐ [C₁₈H₂₁N₃O₂, (III)] derivatives of benzylidene‐4‐hydroxybenzohydrazide, all crystallize in the same space group (P2₁/c), (I) and (II) also being isomorphous. In all three compounds, the conformation about the C=N bond is E. The molecules of (I) and (II) are relatively planar, with dihedral angles between the two benzene rings of 5.75 (12) and 9.81 (17)°, respectively. In (III), however, the same angle is 77.27 (9)°. In the crystal structures of (I) and (II), two‐dimensional slab‐like networks extending in the a and c directions are formed via N—H...O and O—H...O hydrogen bonds. The molecules stack head‐to‐tail viaπ–π interactions involving the aromatic rings [centroid–centroid distance = 3.7622 (14) Å in (I) and 3.8021 (19) Å in (II)]. In (III), undulating two‐dimensional networks extending in the b and c directions are formed via N—H...O and O—H...O hydrogen bonds. The molecules stack head‐to‐head viaπ–π interactions involving inversion‐related benzene rings [centroid–centroid distances = 3.6977 (12) and 3.8368 (11) Å].     

Bi(III)‐catalyzed C―S cross‐coupling reaction

A direct synthetic route for the C―S coupling of aryl halides with thiophenols is described. This method is tolerant to electron‐withdrawing and electron‐donating functional groups and also to the presence of functional groups in the ortho position of the aryl iodide or thiophenol. Aryl iodides are coupled with thiophenols without affecting the other functionalities present in the aryl ring. These reactions follow second‐order kinetics. Copyright © 2012 John Wiley & Sons, Ltd.     

(±)‐2‐Aryl‐2,3‐dihydro‐4(1H)‐quinolinones by a tandem reduction–Michael addition reaction

An efficient synthesis of (±)‐2‐aryl‐2,3‐dihydro‐4(1H)‐quinolinones has been developed from chalcones prepared from 2′‐nitroacetophenone and a series of substituted benzaldehydes. The cyclization sequence is initiated by reduction of the nitro group under dissolving metal conditions using iron powder in concentrated hydrochloric acid. Milder conditions, using acetic acid or acetic acid–phosphoric acid as the reaction medium, were less satisfactory. Procedural details as well as a mechanistic discussion and reaction optimization studies are presented. J. Heterocyclic Chem., (2011).     

New Chiral Reagent for Installation of Pharmacophoric (S)‐ or (R)‐2‐(Alkoxyphosphono)‐1‐amino‐2,2‐difluoroethyl Groups

A new chiral reagent has been developed for generalized installation of pharmacophoric (S)‐ or (R)‐2‐(alkoxyphosphono)‐1‐amino‐2,2‐difluoroethyl group into organic compounds. The original synthetic application of this new reagent is exemplified by Friedel–Crafts reactions with indoles, which proceed efficiently with excellent diastereoselectivity to give enantiomerically pure products.     

[μ3‐cis‐N‐(2‐Aminoethyl)‐N′‐(2‐carboxylatophenyl)oxamidato(3−)]bis(2,2′‐diamino‐4,4′‐bi‐1,3‐thiazole)tetracopper(II) bis(2,4,6‐trinitrophenolate)

The title complex, [Cu₄(C₁₁H₁₀N₃O₄)₂(C₆H₆N₄S₂)₂](C₆H₂N₃O₇)₂, consists of a circular tetracopper(II) cation with an embedded inversion centre and two uncoordinated picrate (2,4,6‐trinitrophenolate) anions. The Cu^II cations at the inner sites of N‐(2‐aminoethyl)‐N′‐(2‐carboxylatophenyl)oxamidate(3−) (oxbe) have square‐planar environments and those at the outer sites are in square‐pyramidal geometries. The separations of pairs of Cu^II cations bridged by cis‐oxamide and carboxylate groups are 5.2217 (5) and 5.2871 (5) Å, respectively. The tetracopper(II) cations and picrate anions are connected by N—H...O hydrogen bonds into a two‐dimensional network parallel to the (010) plane, and these two‐dimensional networks are assembled by two types of π–π stacking interactions into a three‐dimensional supramolecular structure.     

An efficient and green synthesis of 3,3′‐benzylidenebis (4‐hydroxy‐6‐methylpyridin‐2(1H)‐one) derivatives through multi‐component reaction in ionic liquid

A series of new 3,3′‐benzylidenebis(4‐hydroxy‐6‐methylpyridin‐2(1H)‐one) derivatives were synthesized via a three‐component reaction of an aldehyde, an aniline or ammonium acetate and 6‐methyl‐4‐hydroxypyran‐2‐one in ionic liquid. These heterocyclic compounds produced could be conveniently separated from the reaction mixture without any volatile organic solvents, and the ionic liquid could be readily reused without efficiency loss after simple treatment.