Comparison of the reaction pathways and intermediate products of a microwave-assisted and high-pressure-promoted cycloaddition of vinyl-moiety-containing dienophiles on 2H-pyran-2-ones

A comparative study of the reaction pathway of the cycloaddition of various vinyl-containing dienophiles on a set of substituted 3-acylamino-2H-pyran-2-ones under microwave-assisted and high-pressure conditions is presented. In the course of the reaction both the intermediate products, i.e., the 2-oxabicyclo[2.2.2]oct-5-ene (the exo/endo selectivity depended upon the dienophile) and the alkoxycyclohexadiene systems, were isolated and comprehensively characterized; this included X-ray diffraction analyses. The role of the base (DABCO) as an organocatalyst was further elucidated.     

Construction of a New Class of Tetracycline Lead Structures with Potent Antibacterial Activity through Biosynthetic Engineering

Antimicrobial resistance and the shortage of novel antibiotics have led to an urgent need for new antibacterial drug leads. Several existing natural product scaffolds (including chelocardins) have not been developed because their suboptimal pharmacological properties could not be addressed at the time. It is demonstrated here that reviving such compounds through the application of biosynthetic engineering can deliver novel drug candidates. Through a rational approach, the carboxamido moiety of tetracyclines (an important structural feature for their bioactivity) was introduced into the chelocardins, which are atypical tetracyclines with an unknown mode of action. A broad‐spectrum antibiotic lead was generated with significantly improved activity, including against all Gram‐negative pathogens of the ESKAPE panel. Since the lead structure is also amenable to further chemical modification, it is a platform for further development through medicinal chemistry and genetic engineering.     

A method for computing lowest eigenvalues of symmetric polynomial differential operators by semidefinite programming

A method for computing global minima of real multivariate polynomials based on semidefinite programming was developed by N.Z. Shor, J.B. Lasserre and P.A. Parrilo. The aim of this article is to extend a variant of their method to noncommutative symmetric polynomials in variables X and Y satisfying YX−XY=1 and X^*=X, Y^*=−Y. Global minima of such polynomials are defined and showed to be equal to minima of the spectra of the corresponding differential operators. We also discuss how to exploit sparsity and symmetry. Several numerical experiments are included. The last section explains how our theory fits into the framework of noncommutative real algebraic geometry.     

3-(5-Amino-1,2,4-triazole)-1,2,4-oxadiazole: A new biheterocyclic scaffold for the synthesis of energetic materials

Nitrogen-rich heterocycles are increasingly used in energetic chemistry with the aim to achieve superior performance of the new energetic materials. Combining such building blocks into biheterocycles increases energy output while at the same time retains low sensitivity. Herein, we report the synthesis and characterization of a compound containing a 5-amino-1,2,4-triazole moiety connected with a 1,2,4-oxadiazole ring. The trichloromethyl group attached to the oxadiazole ring offers an attractive point for further transformations into potentially energetic compounds.     

HPTLC–densitometric and HPTLC–MS methods for analysis of flavonoids

HPTLC silica gel plates without and with fluorescence indicator F₂₅₄ in combination with n-hexane–ethyl acetate–formic acid (20:19:1, v/v/v) as a developing solvent were explored for the HPTLC–densitometric and HPTLC–MS/(MSⁿ) analyses of flavonoids. Pre-development of the plates with chloroform–methanol (1:1, v/v) was needed for reliable HPTLC–densitometric analyses of flavonoid aglycones in the whole R_F range, while 2-step pre-development (1^st methanol–formic acid (10:1, v/v), 2^nd methanol), that decreased background signals of formic acid adducts, was required for HPTLC–MS analyses. Optimization with conditioning of the adsorbent layer with water before development and saturation of the twin trough chamber resulted in required decrease of the R_F values of studied flavonoids (flavone, apigenin, luteolin, chrysin, quercetin dihydrate, myricetin, kaempferide, kaempferol, naringenin, pinocembrin).

Detection was performed based on fluorescence quenching (on the plates with F₂₅₄), natural fluorescence and after post-chromatographic derivatization with natural product reagent without or with further enhancement and stabilization of fluorescent zones with polyethylene glycol (PEG 400 or PEG 4000) or paraffin–n-hexane reagents. For all three reagents, drying temperature and time passed after drying influenced the intensity, which was increasing the first 20?min, and the stability (less than 2?h for PEGs and at least 24?h for paraffin–n-hexane) of the standards’ zones.

Optimal wavelengths for densitometric evaluation were selected based on in-situ absorption spectra scanned before and after derivatization and after stabilization. The developed method was tested via analyses of propolis, roasted coffee, rose hip, hibiscus, rosemary and sage crude extracts. To further increase the reliability of the obtained densitometric results HPTLC–MS/(MSⁿ) analyses of all crude extracts were performed. Several phenolic and non-phenolic compounds were tentatively identified.

Some possible interferences with phenolic acids (chlorogenic acid, rosmarinic acid, protocatechuic acid, gallic acid, syringic acid, ellagic acid, trans-cinnamic acid, o-coumaric acid, m-coumaric acid, p-coumaric acid, caffeic acid, ferulic acid, sinapic acid) that are often present in the extracts together with flavonoids were also examined.     

An expedient route to indoles via a cycloaddition/cyclization sequence from (Z)-1-methoxybut-1-en-3-yne and 2H-pyran-2-ones

The cycloaddition of (Z)-1-methoxybut-1-en-3-yne (2) with 5,6-disubstituted 3-acylamino-2H-pyran-2-ones 1 under microwave-irradiation conditions, with classical heating or at high-pressures (13-15 kbar) affords the benzene derivatives 3 with a strategically positioned 2-methoxyethenyl moiety. In some cases, at high-pressures after long reaction times, 2,2-dimethoxyethyl products 4 were obtained. Adducts 3 and 4 can be cyclized under mild conditions into 1,5,6-trisubstituted indole derivatives 5.     

Synthesis and Crystal Structures of Methyl 3-(Benzoylamino)-6-methyl-2-oxo-2<Emphasis Type="Italic">H</Emphasis>-pyran-5-carboxylate and <Emphasis Type="Italic">N</Emphasis>-[5-(3,4-Dimethoxyphenyl)-6-methyl-2-oxo-2<Emphasis Type="Italic">H</Emphasis>-pyran-3-yl]benzamide

Abstract  

The compounds methyl 3-(benzoylamino)-6-methyl-2-oxo-2H-pyran-5-carboxylate (1), C₁₅H₁₃NO₅, and N-[5-(3,4-dimethoxyphenyl)-6-methyl-2-oxo-2H-pyran-3-yl]benzamide (2), C₂₁H₁₉NO₅, crystallize as a centrosymmetric hydrogen-bonded dimer facilitated by N–H···O interactions involving the amide and carbonyl moiety of the lactone group of adjacent molecules. Supramolecular aggregation in 1 is controlled by a combination of π–π interactions [centroid–centroid distance = 4.0745(11) ?] and weak C–H···O hydrogen bonding between the phenyl ring of the benzoylamino group and the carbonyl atom of the methoxycarbonyl group and in 2 by a combination of π–π interactions [centroid–centroid distance = 4.0699(8) and 4.1556(10) ?], weak C–H···O interactions between the methoxy substituents of the adjacent dimethoxyphenyl group and weak C–H··· π interactions.     

Apparent Molar Volume and Apparent Molar Expansibility of Rubidium, Cesium, and Ammonium Cyclohexylsulfamate in Aqueous Solution

Summary. The apparent molar volume of rubidium, caesium, and ammonium cyclohexylsulfamate was determined from the density data of their aqueous solutions at 293.15, 298.15, 303.15, 313.15, 323.15, and 333.15 K. From the apparent molar volume, determined at various temperatures, the apparent molar expansibility was calculated. The limiting apparent molar volume and apparent molar expansibility were evaluated and apportioned into their ionic components. The limiting partial molar ionic volumes and expansibilities are discussed in terms of the various effects of the ion in solution on the structure of water. It was shown that the limiting partial molar ionic expansibilities of the alkali-metal cations increase with their ionic radii. The coefficients of thermal expansion of the investigated solutions at 298.15 K were calculated and are presented graphically together with some alkali-metal cyclohexylsulfamates and tetramethylammonium cyclohexylsulfamate. The densities of the investigated solutions can be adequately represented by an equation derived by Redlich.     

Guanine alkylation by ethylene oxide: calculation of chemical reactivity

In this paper we report on calculations of the activation free energy for a chemical reaction between ethylene oxide and guanine. Ethylene oxide is biologically relevant per se and is also a model compound for numerous ultimate carcinogens. Calculations were performed on the medium-high ab initio, DFT, and semiempirical MO levels. Effects of solvation were considered using the Langevine dipole method and solvent reaction field method of Tomasi and co-workers. The calculated activation free energies are in reasonable agreement with the experimental value.