Robust synthesis of C-terminal cysteine-containing peptide acids through a peptide hydrazide-based strategy.

A new robust strategy was reported for the epimerization-free synthesis of C-terminal Cys-containing peptide acids through mercaptoethanol-mediated hydrolysis of peptide thioesters prepared in situ from peptide hydrazides. This simple-to-operate and highly efficient method avoids the use of derivatization reagents for resin modification, thus providing a practical avenue for the preparation of C-terminal Cys-containing peptide acids.

Princípios básicos para produção de silagem / Basic principles for silage production / Principios básicos para la producción de ensilaje

Conservar alimentos na forma de silagem possui grande valia em regiões que ocorre estacionalidade climática, onde o excedente de forragem produzido no período das águas poderá ser utilizado posteriormente na época de estiagem. Para se produzir silagem de qualidade é preciso atentar-se para vários fatores inerentes ao método como também a planta forrageira a ser utilizada. Assim, conhecer os princípios básicos para produção de silagem são de grande valia para se produzir volumoso conservado de qualidade. Objetivou-se apresentar nesta revisão abordar os conceitos sobre a produção de silagem, como também as alterações que ocorrem durante o processo fermentativo. As principais características químicas avaliadas na silagem são: composição química, pH, capacidade tampão, as concentrações de ácidos orgânicos (ácidos láctico, acético, propiônico e butírico) e o nitrogênio amoniacal sob o percentual de nitrogênio total. Conhecer adequadamente as etapas para a produção de silagem são de grande valia para entender como funciona o processo fermentativo e como pode ser maximizado, resultando em silagem de qualidade e consequentemente satisfatório desempenho animal. Logo, com as informações expostas sobre o processo de conservação de forragens na forma de silagem consegue-se adequar a cultura forrageira à técnica, obtendo-se silagens de qualidade.(AU)

Preserving food in the form of silage has great value in regions presenting climatic seasonality, where the surplus of forage produced in the rainy season can be used later in the dry season. In order to produce quality silage, several factors inherent to the method must be considered, as well as the forage plant being used. Thus, knowing the basic principles for silage production is of great value to produce quality bulky preserves. The purpose of this review was to discuss concepts regarding the production of silage as well as the changes that occur during the fermentation process. The main chemical characteristics evaluated in the silage are chemical composition, pH, buffer capacity, organic acid concentrations (lactic, acetic, propionic and butyric acids), and ammoniacal nitrogen under the percentage of total nitrogen. Knowledge of the proper steps for silage production is of great value in understanding how the fermentation process takes place and how to maximize it, resulting in quality silage and consequently satisfactory animal performance. Thus, with the information presented on the process of forage preservation in silage form it is possible to adapt the forage culture to the specific technique, getting it quality silage.(AU)

Conservar alimentos en forma de ensilaje tiene gran valor en regiones que ocurre estacionalidad climática, donde el excedente de forraje producido en el período de las aguas podrá ser utilizado posteriormente en la época de sequía. Para producir ensilaje de calidad es necesario atentarse para varios factores inherentes al método, como también a la planta forrajera a ser utilizada. Así, conocer los principios básicos para la producción de ensilaje es de gran valor para producir abultado conservado de calidad. Se pretendió presentar en esta revisión los conceptos sobre la producción de ensilaje, así como las alteraciones que ocurren durante el proceso fermentativo. Las principales características químicas evaluadas en el ensilaje son: composición química, pH, capacidad tampón, las concentraciones de ácidos orgánicos (ácidos láctico, acético, propiónico y butírico) y el nitrógeno amoniacal bajo el porcentaje de nitrógeno total. Conocer las etapas adecuadamente para la producción de ensilaje es de gran valor para entender cómo funciona el proceso fermentativo y cómo puede ser maximizado, resultando en ensilaje de calidad y consecuentemente satisfactorio desempeño animal. Por lo tanto, con las informaciones expuestas sobre el proceso de conservación de forrajes en la forma de ensilaje, es posible adaptar el cultivo de forrajera a la técnica, conseguirlo ensilajes de calidad.(AU)

Amide Bond Activation of Biological Molecules.

Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide bonds is their ability to form resonating structures, thus, they are highly stable and adopt particular three-dimensional structures, which, in turn, are responsible for their functions. The main focus of this review article is to report the methodologies for the activation of the unactivated amide bonds present in biomolecules, which includes the enzymatic approach, metal complexes, and non-metal based methods. This article also discusses some of the applications of amide bond activation approaches in the sequencing of proteins and the synthesis of peptide acids, esters, amides, and thioesters.

Acylated Glycosidic Acid Methyl Esters Generated from the Convolvulin Fraction of Rhizoma Jalapae Braziliensis by Treatment with Indium(III) Chloride in Methanol.

Four hexaglycosides of methyl 3S,12S-dihydroxyhexadecanoate (1-4) were provided after treatment of the crude convolvulin fraction from Rhizoma Jalapae Braziliensis (the root of Ipomoea operculata (GOMES) MART., Convolvulaceae) with indium(III) chloride in methanol. The structures of 1-4 were elucidated on the basis of spectroscopic and chemical methods. Their sugar moieties were partially acylated with organic acids including (3S,9R)-3,6:6,9-diepoxydecanoic (exogonic) acid, (E)-2-methylbut-2-enoic (tiglic) acid, and isovaleric acid.

Isotetronic acids from an oxidative cyclization.

Oxidation of α,ß-unsaturated methyl ketones with selenium dioxide leads to a cascade of reactions culminating in the formation of isotetronic acids.

Synthesis and characterization of polyacids from palm acid oil and sunflower oil via addition reaction.

In this study aliphatic polyacids were synthesized using palm acid oil (PAO) and sunflower oil (SFO) via addition reaction technique. The synthesized materials were characterized using Fourier-transform infra-red (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS) and thermo-gravimetric analysis (TGA). Mixing formic acid and hydrogen peroxide with PAO or SFO at the ratio 3:10:1 produced the lowest iodine value of 10.57 and 9.24 respectively, indicating the increase in epoxidization of both oils. Adding adipic acid to the epoxidized oils at a ratio of 1:10 increases the acid values of SFO and PAO to 11.22 and 6.73 respectively. The existence of multi-acid groups present in synthesized polyacid was confirmed by MALD-ToF-MS. This feature indicates a possible value to the biomaterials development.

Sugar furanoid trans-vicinal diacid as a γ-turn inducer: synthesis and conformational study.

A simple method for the synthesis of a sugar furanoid trans vicinal diacid and its incorporation into the N-terminal tetrapeptide sequence (H-Phe-Trp-Lys-Thr-OH) to get glycopeptide has been described. 2D NMR and MD simulation studies of clearly show that the sugar diacid adopts a γ-turn conformation towards the N-terminus.

Facile synthesis of highly efficient and recyclable magnetic solid acid from biomass waste.

In this work, sawdust, a biomass waste, is converted into a magnetic porous carbonaceous (MPC) solid acid catalyst by an integrated fast pyrolysis-sulfonation process. The resultant magnetic solid acid has a porous structure with high surface area of 296.4 m(2) g(-1), which can be attributed to the catalytic effect of Fe. The catalytic activity and recyclability of the solid acid catalyst are evaluated during three typical acid-catalyzed reactions: esterification, dehydration, and hydrolysis. The favorable catalytic performance in all three reactions is attributed to the acid's high strength with 2.57 mmol g(-1) of total acid sites. Moreover, the solid acid can be reused five times without a noticeable decrease in catalytic activity, indicating the stability of the porous carbon (PC)-sulfonic acid group structure. The findings in the present work offer effective alternatives for environmentally friendly utilization of abundant biomass waste.

Asymmetric Ti-crossed Claisen condensation: application to concise asymmetric total synthesis of alternaric acid.

Asymmetric Ti-crossed Claisen condensation utilizing the dioxane-2,5-dione chiral template and its successful application to total synthesis of chiral alternaric acid are described.

Novel acid mono azo dye compound: synthesis, characterization, vibrational, optical and theoretical investigations of 2-[(E)-(8-hydroxyquinolin-5-yl)-diazenyl]-4,5-dimethoxybenzoic acid.

Novel acid mono azo dye, 2-[(E)-(8-hydroxyquinolin-5yl)-diazenyl]-4,5-dimethoxybenzoic acid (HQD), was synthesized by coupling diazonium salt solution of 2-amino-4,5-dimethoxybenzoic acid (DMA) with 8-hydroxyquinoline (HQ). This dye was characterized by UV-vis, IR & Raman, (1)H and (13)C NMR spectroscopic techniques and elemental analysis. The normal coordinate analysis of HQD was also performed to assign each band in vibrational spectra. DFT (B3LYP and B3PW91) calculations were employed to optimize the geometry, to interpret NMR spectra, to calculate and to determine the stable tautomeric structure of the compound. Natural Bond Orbital (NBO) analysis was performed to investigate intramolecular interactions. The vibrational spectral data obtained from solid phase IR & Raman spectra were assigned based on the results of the theoretical calculations. UV-vis spectroscopic technique was employed to obtain the optical band gap of HQD. The analysis of the optical absorption data revealed the existence of direct and indirect transitions in the optical band gaps. The optical band gaps of HQD have been found 1.95 and 1.90eV for direct and indirect transitions, respectively.

Investigation of the reaction impurities associated with methylamphetamine synthesized using the Nagai method.

The synthesis of methylamphetamine hydrochloride from l-ephedrine or d-pseudoephedrine hydrochloride via reduction with hydriodic acid and red phosphorus was investigated. Eighteen batches of methylamphetamine hydrochloride were synthesized in six replicate batches using three different reaction times. This allowed the investigation of the variation of impurities in the final product with reaction time. The results obtained have resolved previously conflicting impurity profile data reported in the literature for this synthesis route. The impurity profile was shown to change with reaction time, and all previously reported impurity components were identified but not in all batches. Additionally, 20 batches of methylamphetamine hydrochloride were synthesized from either from l-ephedrine or d-pseudoephedrine hydrochloride in reactions which were allowed to proceed for 24 h. The impurities present in the resulting batches were investigated, and route-specific impurities present in all batches were identified. Batch-to-batch fluctuations in the resultant chromatographic impurity profile, despite careful synthetic monitoring and control, were also noted.

Synthesis and characterization of privileged monodentate phosphoramidite ligands and chiral Brønsted acids derived from d-mannitol.

The synthesis of several novel chiral phosphoramidite ligands (L1-L8) with C(2) symmetric, pseudo C(2) symmetric secondary amines and chiral Brønsted acids 1a,b has been achieved. These chiral auxiliaries were obtained from commercially available d-mannitol, and secondary amines in moderate to excellent yields. Excellent diastereoselectivites of ten chiral auxiliaries were obtained. The chiral phosphoramidite ligands and chiral Brønsted acids were fully characterized by spectroscopic methods.

Synthesis and SAR optimization of diketo acid pharmacophore for HCV NS5B polymerase inhibition.

Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Here we report the synthesis and biological evaluation of a new series of α,γ-diketo acids (DKAs) as NS5B polymerase inhibitors. We initiated structure-activity relationship (SAR) optimization around the furan moiety of compound 1a [IC(50) = 21.8 µM] to achieve more active NS5B inhibitors. This yielded compound 3a [IC(50) = 8.2 µM] bearing the 5-bromobenzofuran-2-yl moiety, the first promising lead compound of the series. Varying the furan moiety with thiophene, thiazole and indazole moieties resulted in compound 11a [IC(50) = 7.5 µM] bearing 3-methylthiophen-2-yl moiety. Finally replacement of the thiophene ring with a bioisosteric phenyl ring further improved the inhibitory activity as seen in compounds 21a [IC(50) = 5.2 µM] and 24a [IC(50) = 2.4 µM]. Binding mode of compound 24a using glide docking within the active site of NS5B polymerase will form the basis for future SAR optimization.

NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold.

Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay. The modulatory activity was observed for acidic moieties and metabolically labile esters only, which supports our hypothesis of an acid-lysine interaction to be relevant for this type of γ-secretase modulators.

Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors.

Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2' subsite within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported.

Synthesis and anion affinity of a bidendate sulfonium fluorosilane Lewis acid.

The cationic fluorosilane [1-Ant(2)FSi-2-Me(2)S-(C(6)H(4))](+) (2(+)) readily complexes fluoride ions to afford the corresponding zwitterionic difluorosilicate complex 1-Ant(2)F(2)Si-2-Me(2)S-(C(6)H(4)) (2-F) with a binding constant in CHCl(3) of 7 (+/-1) x 10(6) M(-1). Structural and computational results indicate that the high fluorophilicity of 2(+) arises from both Coulombic and cooperative effects reflected by the formation of a Si-F-->S bridge with a F-->S distance of 2.741(3) A.

Kinetics of resin-supported Mitsunobu esterification and etherification reactions.

Solid-phase Mitsunobu reaction is very useful in organic and parallel synthesis. In this work, we optimize the solid-phase Mitsunobu esterification and etherification reactions and investigated their kinetics by single-bead FTIR microspectroscopy method. Thirteen solid-phase Mitsunobu esterification reactions proceeded at rates between 2.5 x 10(-3) and 19 x 10(-3) s(-1), while five etherification reactions at generally slower rates between 3.3 x 10(-3) and 8.9 x 10(-3) s(-1). We discovered that reaction rates, as in solution phase Mitsunobu reactions, linearly correlated to pK(a) values of acids and phenols used in the reaction. By studying side reactions and intermediates, we found that the solid-phase reaction mechanism also bears remarkable similarities to that of solution phase Mitsunobu reaction.

Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches.

Of the concepts used to improve the efficiency of organic syntheses, two have been especially effective: atom economy (the use of routes in which most of the atoms present in the reactants also end up in the product) and chemoselectivity (the use of reactions that take place only at desired positions in a molecule). Synthesis of complex natural products is the most demanding arena in which to explore such principles. The bryostatin family of compounds are especially interesting targets, because they combine structural complexity with promising biological activity. Furthermore, synthetic routes to some bryostatins have already been reported, providing a benchmark against which new syntheses can be measured. Here we report a concise total synthesis of bryostatin 16 (1), a parent structure from which almost all other bryostatins could in principle be accessed. Application of atom-economical and chemoselective reactions currently under development provides ready access to polyhydropyran motifs in the molecule, which are common structural features of many other natural products. The most notable transformations are two transition-metal-catalysed reactions. The first is a palladium-catalysed reaction of two different alkynes to form a large ring. The product of this step is then converted into a dihydropyran (the 'C ring' of bryostatins) in the second key reaction, which is catalysed by a gold compound. Analogues of bryostatin that do not exist in nature could be readily made by following this route, which might allow the biological activity of bryostatins to be fine-tuned.