A novel approach to Morita-Baylis-Hillman (MBH) lactones via the Lewis acid-promoted couplings of α,β-unsaturated lactone with aldehydes

The Morita-Baylis-Hillman (MBH)-type reaction of α,β unsaturated δ-lactone with various aldehydes has been achieved without the direct use of a Lewis base. The new MBH process can be conveniently carried out by the slow addition of the diethylaluminum iodide into the solution of lactone and aldehyde in dichloromethane at 0°C. Modest to good yields were obtained (50-65%) for eight examples.     

Studies on the Stereochemistry of 2-(Nitromethylidene)-Heterocycles

The ¹H-NMR spectra of 2-(nitromethylidene)pyrrolidine ( 7 ), 1-methyl-2-(nitromethylidene)imidazolidind ( 10 ) and 3-(nitromethylidene)tetrahydrothiazine ( 11 ) in CDCl₃ and (CD₃)₂SO indicate that these compounds have the intramolecularly H-bonded structures (Z)- 7 , (E)- 10 and (Z)- 11 while the N-methyl derivative 8 of 7 is (E)-configurated in both solvents. 1-Benzylamino-1-(methyltio)-2-nitroehtylene ( 13 ), an acylic model, has the H-bonded configuration (E)- 13 in CDCl₃ and in (CD₃)₂SO. 2-(Nitromethylidene)thiazolidine ( 3 ) has the (E)-configuration in CDCl₃ but exists in (CD₃)₂SO as a mixture of (Z)- and (E)-isomers with the former predominating. Both species are detected to varying proportions in a mixture of the two solvents. ¹⁵N-NMR spectroscopy of 3 ruled out unambiguously the nitronic acid structure 6 and the nitromethyleimine structure 5 . The N-methyl derivative 4 of 3 is (Z)-configurated in (CD₃)₂SO. Comparison of the olefinic proton shifts of (Z)- 3 and (Z)- 4 with those of analogues and also of 1,1-bis(methylti)-2-nitroethylene ( 12 ) shows decreased conjugation of the lone pair of electrons of the ring N-atom in (Z)- 3 and (Z)- 4 . This is also supported by ¹³C-NMR studies. Plausible explanations for the phenomenon are offered by postulating that the ring N-atoms are pyramidal in (Z)- 3 and (Z)- 4 and planar in other cases or, alternatively, that the conjugated nitroenamine system gets twisted due to steric interaction between the NO₂-group and the ring S-atom. Single-crystal X-ray studies of 3 and 8 show that the former exists in the (Z)-configuration and the latter in (E)-configuration; the ring N-atom in the former has slightly more pyramidal character than in the latter.     

Antioxidant enzymes activity in subcellular fraction of freshwater prawnsM. malcolmsonii andM. lamarrei lamarrei

Subcellular distribution of Superoxide dismutase (SOD), catalase (CAT), selenium (SC) dependent glutathione peroxidase, and Se-independent glutathione peroxidase (GSH-Px) activities were detected in different tissues (hepatopancreas, muscle, and gill) of freshwater prawnsMacrobrachium malcolmsonii andMacrobrahium lamarrei lamarrei. CAT and SOD were found almost equally between the mitochondrial and cytosolic fraction. Both Se-dependent and Se-independent GSH-Px activities were mainly found in cytosolic fraction.     

Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria

Antibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial protein catalyzed capture agent (PCC) technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant Klebsiella pneumoniae, an opportunistic Gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of K. pneumoniae for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC₅₀ ∼50 nM) to full-length MrkA, and selectively bound to MrkA-expressing K. pneumoniae, but not to other pathogenic bacterial species. AR-PCCs that bear a hapten moiety promoted antibody recruitment to K. pneumoniae, leading to enhanced phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria.

Antibody-recruiting protein-catalyzed capture agent (AR-PCCs) are a new class of all-synthetic and highly targeted antibiotics that recruit endogenous immune responses to eliminate drug-resistant microbes.     

Recent developments in the chemistry of perhydroindoles and perhydrocinnolines

Recent synthetic routes to the tetrahydro, hexahydro and octahydro derivatives of indoles are reviewed. An interesting one is the formation of 3-amino-4-oxo-4,5,6,7-tetrahydroindoles in the reaction of 2-phenacyl cyclohexane-l,3-diones with 1,1-disubstituted hydrazines. Antifertility, cns depressant and antiinflammatory activities have been encountered for perhydroindoles besides other biological activities. Hexahydrocinnolines are obtained from the reaction of 2-phenacyl (acetonyl) cyclohexanones and cyclohexane-1,3-diones with hydrazines, while octahydrocinnolines are formed from cyclohexanone-2-acetic acids and hydrazines in two steps. 5-oxo-5,6,7,8-hexahydrocinnolines and their oximes undergo anomalous and interesting aromatisation reactions. Some hexahydrocinnolines are cns depressants while octahydrocinnolines are analgesics. More importantly, they are precursors for interesting azamorphinans. Contribution No. 736 from Research centre     

Konstante der potentiellen Energie und mittlere Schwingungsamplituden in einigen XY4-Molekülen und-Ionen tetraedrischer Symmetrie

Zusammenfassung Mit Hilfe der gruppentheoretischen Methode vonWilson wurden die Konstanten der potentiellen Energie für die Tetramethylverbindungen und-ionen der Elemente der 4. und 5. Gruppe, besonders des C, Si, Ge, Sn, Pb, N, As und Sb, sowie auch der Aluminat- und Zinkat-Ionen unter Verwendung eines Valenzkraftfeldes mit 5 Konstanten berechnet. Auf der Grundlage der vonCyvin postulierten Symmetriekoordinaten wurden die Größen der mittleren Amplitudenquadrate und die mittleren Schwingungsamplituden für gebundene und nicht-gebundene Atompaare bei den Temperaturen 298° K und 500° K berechnet. Der geringfügige Einfluß der Schwingungen der Methyl- und Hydroxylgruppen auf die Gerüstschwingungen wurde vernachlässigt, jedoch die nicht-diagonalen Elemente bei der Lösung der Säkulargleichungen in Betracht gezogen.

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Potential energy constants and mean amplitudes of vibration in some XY₄-molecules and-ions with tetrahedral symmetry

Potential energy constants have been evaluated by theWilson's group theoretical method for the tetramethyl compounds and ions of the elements of the fourth and fifth groups, namely, C, Si, Ge, Sn, Pb, N, As, and Sb as well as the aluminate and zincate ions employing a five-constant valence force field. On the basis of the symmetry coordinates postulated byCyvin, the mean-square amplitude quantities and mean amplitudes of vibration for the bonded and nonbonded atom pairs have also been computed at the temperatures 298° K and 500° K. The effect of the vibrations of methyl and hydroxyl groups on the skeletal modes, being small, has been neglected and the off-diagonal element has been taken into account in solving the secular equations.

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Diese Arbeit wurde vom US-Army Research Office, Durham, unter der Nummer AROD-31-124-6864 unterstützt.     

含水合物沉积物多相渗流特性研究进展

天然气水合物作为一种储量大、无污染的清洁能源近些年受到了广泛关注.近20年来,中国进行了较大范围的陆海域天然气水合物储层勘探与储量预测. 2017年,中国地质调查局牵头对南海神狐海域的天然气水合物进行了基于降压渗流原理的试验性开采.国内外已进行的水合物试采工程面临着气体产量低、出砂较多等问题,其最主要的原因之一是开发过程中沉积物内复杂多相渗流机理尚不明晰.本文综述了平行毛细管模型、Kozeny模型等广泛应用于天然气水合物开发渗流分析的理论模型,对比分析了水合物开发多尺度渗流过程模拟方法,简述了国内外含水合物沉积物渗透率测试、渗流过程中沉积物物性演变以及水合物开采室内模拟等方面的渗流实验进展,总结了矿场尺度的天然气水合物储层开采过程中产气数值模拟手段,展望了多相渗流模型、储层原位含水合物样品室内测试及结构与物性演化、矿场尺度数值模拟与水平井压裂技术等应用研究的未来方向与挑战.