Photo- and radiation chemical induced degradation of lignin model compounds

The basic mechanistic aspects of the photo- and radiation chemistry of lignin model compounds (LMCs) are discussed with respect to important processes related to lignin degradation. Several reactions occur after direct irradiation, photosensitized or radiation chemically induced oxidation of LMCs. Direct irradiation studies on LMCs have provided supportive evidence for the involvement of hydrogen abstraction reactions from phenols, beta-cleavage of substituted alpha-aryloxyacetophenones and cleavage of ketyl radicals (formed by photoreduction of aromatic ketones or hydrogen abstraction from arylglycerol beta-aryl ethers) in the photoyellowing of lignin rich pulps. Photosensitized and radiation chemically induced generation of reactive oxygen species and their reaction with LMCs are reviewed. The side-chain reactivity of LMC radical cations, generated by radiation chemical means, is also discussed in relation with the enzymatic degradation of lignin.     

Efficient palladium-catalyzed cross-coupling of beta-chloroalkylidene/arylidene malonates using microwave chemistry

A general method for the synthesis of beta-aryl/alkylarylidene malonates is reported. The key step involves the coupling of an arylboronic acid to a beta-chloroalkyl/arylidene malonate, in the presence of K2CO3 and 1 mol % of the air-stable palladium catalyst (POPd) under microwave irradiation, to afford beta-aryl/alkylarylidene malonates in good yields. The combination of mild reaction conditions, air stable catalyst, microwave-enhanced chemistry, and high levels of functional group compatibility make this an attractive synthetic approach to this class of compounds.     

Synthetic Applications of the beta-Lithiation of beta-Aryl Secondary Amides: Diastereoselective and Enantioselective Substitutions

The sequence of beta-lithiation and electrophilic substitution of beta-aryl secondary amides is reported. The lithiations occur regioselectively at the beta-position, and the resulting lithiated intermediates can be reacted with a wide range of electrophiles to give substituted products. Reactions of beta-lithiated amides bearing an alpha-substituent provide substituted products with high diastereoselectivity. Electrophilic substitutions of beta-lithiated N-methylamides in the presence of the chiral diamine (-)-sparteine provide highly enantioenriched products. The methodology is used to synthesize enantioenriched beta-aryl beta-substituted amides, acids, and lactones.     

Catalytic enantioselective conjugate addition of cyanide to alpha,beta-unsaturated N-acylpyrroles

A catalytic enantioselective conjugate addition of cyanide to alpha,beta-unsaturated N-acylpyrroles was developed using the chiral gadolinium catalyst generated from Gd(OiPr)3 and d-glucose-derived ligand 2. Generally high enantioselectivity was obtained from a wide range of substrates; substrates with beta-aryl and beta-vinyl substituents and alpha,beta-disubstituted substrates can now be used. Using this reaction as a key step, short-step syntheses of several pharmaceuticals and their lead compounds were achieved, including the beta-phenyl-substituted GABA analogue and pregabalin.     

Tandem molybdenum catalyzed hydrosilylations: an expedient synthesis of beta-aryl aldehydes

The synthesis of beta-aryl aldehydes utilizing a tandem molybdenum catalyzed hydrosilylation is described. This new functional group interconversion provides an efficient method for the two-carbon homologation of aryl aldehydes.     

Catalytic conjugate additions of carbonyl anions under neutral aqueous conditions

The conjugate addition of carbonyl anions catalyzed by thiazolium salts that is fully operative under neutral aqueous conditions has been accomplished. The combination of alpha-keto carboxylates and thiazolium-derived zwitterions produces reactive carbonyl anions in a buffered protic environment that readily undergo conjugate additions to substituted alpha,beta-unsaturated 2-acyl imidazoles. The scope of the reaction has been examined and found to accommodate various alpha-keto carboxylates and beta-aryl substituted unsaturated 2-acyl imidazoles. The optimal precatalyst for this process is the commercially available thiazolium salt 5, a simple analogue of thiamin diphosphate. In this process, no benzoin products from carbonyl anion dimerization are observed. The corresponding 1,4-dicarbonyl compounds can be efficiently converted into esters and amides by way of activation of the N-methylimidazole ring via alkylation.     

The Morita-Baylis-Hillman adducts of beta-aryl nitroethylenes with other activated alkenes: synthesis and anticancer activity studies

The Morita-Baylis-Hillman (MBH) adducts of beta-aryl nitroethylenes with methyl vinyl ketone (MVK) and acrylate, formed in moderate to good yield when mediated by imidazole/LiCl in THF at room temperature, inhibit HeLa cell proliferation by binding to tubulin.     

2D NMR analysis for unambiguous structural elucidation of phenolic compounds formed through reaction between (+)‐catechin and glyoxylic acid

Various phenolic compounds were synthesized in an aqueous–alcoholic solution containing (+)‐catechin and glyoxylic acid which was used as a model of fruit‐derived food browning that usually occurs during aging. After purification by semi‐preparative HPLC, the isolated compounds were subjected to homo‐ and heteronuclear proton and carbon NMR analysis including COSY, TOCSY, ROESY, HSQC and HMBC techniques. These experiments allowed the structural elucidation and complete ¹H and ¹³C NMR assignment of the isolated compounds. The strategies followed for the assignment of all proton and carbon resonances in addition to the linkage site determination are discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

Mesoporous silica anchored Ru catalysts for highly enantioselective hydrogenation of beta-ketoesters

Recyclable and reusable mesoporous silica anchored Ru catalysts based on 4,4'-substituted BINAPs were synthesized and used for the hydrogenation of beta-alkyl beta-ketoesters with up to 98.6% e.e. and beta-aryl beta-ketoesters with up to 95.2% e.e.     

Analysis of ethylene oxide sequences of the acetal copolymer from trioxane and ethylene oxide

An NMR method for the analysis of the ethylene oxide sequence of the acetal copolymer from trioxane and ethylene oxide has not yet been established. We found three novel cyclic compounds composed of 1 mol of ethyelene oxide and 1 mol of trioxane, 2 mol of ethylene oxide and 1 mol of trioxane, and 3 mol of ethylene oxide and 1 mol of trioxane. These compounds gave only one consecutive oxyethylene unit, two consecutive oxyethylene units, and three consecutive oxyethylene units in three consecutive oxymethylene units, respectively, and gave different ¹H NMR spectra for each oxyethylene unit. Considering these data, we synthesized three polymeric model compounds that have one consecutive oxyethylene sequence, two consecutive oxyethylene sequences, and three consecutive oxyethylene sequences in an oxymethylene main chain. By a linear combination of the ¹H NMR spectrum of each oxyethylene unit of the three polymeric model compounds, we succeeded in determining the ethylene oxide sequence by the ¹H NMR method for the copolymer from trioxane and ethylene oxide. Good agreement was observed between the ¹H NMR method and the hydrolysis method for the analysis of the ethylene oxide sequences. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3239–3245, 2001     

Aerobic oxidation reactions catalyzed by vanadium complexes of bis(phenolate) ligands

Vanadium(V) complexes of the tridentate bis(phenolate)pyridine ligand H(2)BPP (H(2)BPP = 2,6-(HOC(6)H(2)-2,4-(t)Bu(2))(2)NC(5)H(3)) and the bis(phenolate)amine ligand H(2)BPA (H(2)BPA = N,N-bis(2-hydroxy-4,5-dimethylbenzyl)propylamine) have been synthesized and characterized. The ability of the complexes to mediate the oxidative C-C bond cleavage of pinacol was tested. Reaction of the complex (BPP)V(V)(O)(O(i)Pr) (4) with pinacol afforded the monomeric vanadium(IV) product (BPP)V(IV)(O)(HO(i)Pr) (6) and acetone. Vanadium(IV) complex 6 was oxidized rapidly by air at room temperature in the presence of NEt(3), yielding the vanadium(V) cis-dioxo complex [(BPP)V(V)(O)(2)]HNEt(3). Complex (BPA)V(V)(O)(O(i)Pr) (5) reacted with pinacol at room temperature, to afford acetone and the vanadium(IV) dimer [(BPA)V(IV)(O)(HO(i)Pr)](2). Complexes 4 and 5 were evaluated as catalysts for the aerobic oxidation of 4-methoxybenzyl alcohol and arylglycerol β-aryl ether lignin model compounds. Although both 4 and 5 catalyzed the aerobic oxidation of 4-methoxybenzyl alcohol, complex 4 was found to be a more active and robust catalyst for oxidation of the lignin model compounds. The catalytic activities and selectivities of the bis(phenolate) complexes are compared to previously reported catalysts.     

Highly efficient synthesis of chiral beta-amino acid derivatives via asymmetric hydrogenation

The Rh-TangPhos complex is an efficient hydrogenation catalyst for making chiral beta-amino acid derivatives. With the Rh-TangPhos system, high enantioselectivities (up to 99.6%) and turnover numbers have been obtained in the hydrogenation of E/Z isomeric mixtures of both beta-alkyl and beta-aryl beta-(acylamino)acrylates. [reaction: see text]     

Four new prenylated flavonoids from the roots of Cudrania tricuspidata

Four new prenylated flavonoids, cudraflavanones E‐F (1–2) and cudraflavones F‐G (6–7), together with eight known compounds were isolated from the roots of Cudrania tricuspidata. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS and CD. Copyright © 2013 John Wiley & Sons, Ltd.     

Asymmetric synthesis of 4,5,6- and 3,4,5,6-substituted azepanes by a highly diastereoselective and enantioselective lithiation-conjugate addition sequence

Asymmetric syntheses of 4,5,6- and 3,4,5,6-substituted azepanes have been achieved by highly diastereoselective and enantioselective (-)-sparteine-mediated asymmetric lithiation-conjugate additions of N-Boc-N-(p-methoxyphenyl)-2,3-substituted allylamines to a beta-aryl alpha,beta-unsaturated ester followed by hydrolysis, cyclization, and reduction. Access to the enantiomeric adduct is provided by an invertive lithiation-stannylation-lithiation sequence.     

Catalytic asymmetric epoxidation of alpha,beta-unsaturated esters using an yttrium-biphenyldiol complex

We succeeded in a catalytic asymmetric epoxidation reaction of alpha,beta-unsaturated esters via a conjugate addition of an oxidant using 2-10 mol % of the yttirium-chiral biphenyldiol catalyst. A variety of substrates with beta-aryl and beta-alkyl substituents were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy esters in up to 97% yield and 99% ee.     

Development and NMR validation of minimal pharmacophore hypotheses for the generation of fragment libraries enriched in heparanase inhibitors

A combined strategy based on the development of pharmacophore hypotheses and NMR approaches is reported for the identification of novel inhibitors of heparanase, a key enzyme involved in tumor metastasis through the remodeling of the subepithelial and subendothelial basement membranes, resulting in the dissemination of metastatic cancer cells. Several pharmacophore hypotheses were initially developed from the most active heparanase inhibitors known to date and, after their application to a pool of 27 known heparanase inhibitors and a database of 1,120 compounds approved by the FDA, a four-point pharmacophore model was selected as the most predictive. This model was subsequently applied to a database of 686 chemical fragments, and a subset of 100 fragments accomplishing completely or partially the four-point model was selected to perform nuclear magnetic resonance experiments to validate the hypothesis. The experimental studies confirmed the reliability of our pharmacophore model, its applicability to in silico databases in order to reduce the number of compounds to be experimentally screened, and the possibility of generating fragment libraries enriched in heparanase inhibitors. Rafael Gozalbes and Silvia Mosulén contributed equally to this work.     

Non-enzymatic reduction of quinone methides during oxidative coupling of monolignols: implications for the origin of benzyl structures in lignins

Lignin is believed to be synthesized by oxidative coupling of 4-hydroxyphenylpropanoids. In native lignin there are some types of reduced structures that cannot be explained solely by oxidative coupling. In the present work we showed via biomimetic model experiments that nicotinamide adenine dinucleotide (NADH), in an uncatalyzed process, reduced a beta-aryl ether quinone methide to its benzyl derivative. A number of other biologically significant reductants, including the enzyme cellobiose dehydrogenase, failed to produce the reduced structures. Synthetic dehydrogenation polymers of coniferyl alcohol synthesized (under oxidative conditions) in the presence of the reductant NADH produced the same kind of reduced structures as in the model experiment, demonstrating that oxidative and reductive processes can occur in the same environment, and that reduction of the in situ-generated quinone methides was sufficiently competitive with water addition. In situ reduction of beta-beta-quinone methides was not achieved in this study. The origin of racemic benzyl structures in lignins therefore remains unknown, but the potential for simple chemical reduction is demonstrated here.     

Tupisteroide A–C,three new polyhydroxylated steroidal constituents from the roots of Tupistra chinensis

Three new steroidal compounds with polyhydroxy groups, tupisteroide A–C (1–3), were obtained from the roots of Tupistra chinensis, together with one known compound (4) that was isolated from this plant for the first time. The structures of tupisteroide A–C were determined on the basis of one‐ and two‐dimensional NMR spectroscopy, including ¹H–¹H Correlation Spectroscopy, Heteronuclear Multiple Bond Correlation, and Heteronuclear Single Quantum Coherence experiments. The isolated compounds were evaluated for their cytotoxic activities against A549, HepG2, and CaSki cancer cell lines in vitro. Among them, compounds 1, 2, and 4 did not show significant inhibitory activity, but compound 3 showed cytotoxicity against A549 cancer cell lines with IC₅₀ values of 25.0 μM. Copyright © 2012 John Wiley & Sons, Ltd.     

用固体核磁共振和电子能谱研究我国高硫煤的结构

用固体ＮＭＲ和ＸＰＳ技术研究了我国三种（广西合山煤、湖南辰溪煤、浙江长广煤）高硫煤的结构特征。由固体ＮＭＲ测试结果计算出煤的十二种结构参数和芳香簇团的大小，获得了三个样品的结构特征及变化规律，由ＸＰＳ测试结果得到了煤中各种不同形态硫、氮的结合能数值。根据前入所做的模型化合物的结果，得知三咱煤中硫元素主要以噻吩硫形态存在，氮元素主要以吡啶和中的形态存在。     

Analysis of the 1H and 13C NMR spectra of bicyclo[6.2.1]undecane ring systems

A detailed NMR analysis with full assignment of the ¹H and ¹³C spectral data for two polycyclic compounds is described. These compounds are derivatives of the product obtained from the pericyclic reaction between cyclopentadiene and tropone. Peculiar intriguing conformational features of these molecules are discussed. Copyright © 2003 John Wiley & Sons, Ltd.