Stereodivergent, Diels-Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application.

Chiral α,β-unsaturated acylammonium salts are novel dienophiles enabling enantioselective Diels-Alder-lactonization (DAL) organocascades leading to cis- and trans-fused, bicyclic γ- and δ-lactones from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe extensions of stereodivergent DAL organocascades to other racemic dienes bearing pendant secondary and tertiary alcohols, and application to a formal synthesis of (+)-dihydrocompactin is described. A combined experimental and computational investigation of unsaturated acylammonium salt formation and the entire DAL organocascade pathway provide a rationalization of the effect of Brønsted base additives and enabled a controllable, diastereodivergent DAL process leading to a full complement of possible stereoisomeric products. Evaluation of free energy and enthalpy barriers in conjunction with experimentally observed temperature effects revealed that the DAL is a rare case of an entropy-controlled diastereoselective process. NMR analysis of diene alcohol-Brønsted base interactions and computational studies provide a plausible explanation of observed stabilization of exo transition-state structures through hydrogen-bonding effects

CONSERVATIVE FLUIDS AND LUBRICANTS BASED ON TURBINE OIL, NITRO, AMIDO AND PARAFFIN WAX

To create conservation fluids and lubricants based on the oil acids and polyethylene polyamine (PEPA) synthesized amidoamines, and based on α-olefins (C12, C14 and C16-C18) and the nitric acids-nitro compounds. Using of amido, nitro and solid n-paraffins in the turbine oil T-30 (Standard 32-74) formulated lubricants and conservation fluid which are tested under different conditions. It is shown that in comparison with the preservative fluid, the preservative lubrication more effective

Analysis of Structure Destroyed Metal after Diffusion Heat Treatment

It was accomplished research of the structure steel which carbonitriding and subsequent heat treatment was exposed for its cause's destruction to discover. For measure quality field of metal were used methods optical, appearing electronic microscopy and X-ray diffraction. Therefore one of the principal problems were research phase composition, grain and dislocation structure of a metal the gear teeth. Mechanism of rising hear cracks in the gear teeth on different stages her making and their trajectories of evolution were determined

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: inVitro Effects on Neuroinflammation and Oxidative Stress

The search for compounds capable of targeting early pathological changes of Alzheimer̀s disease (AD), such as oxidative stress and neuroinflammation, is an important challenge. Gracilin A derivatives were recently synthesized, using a pharmacophore-directed retrosynthesis (PDR) strategy, and found to possess potent neuroprotective effects. In this work, the previously described derivatives 1–7 which demonstrated mitochondrial-mediated, antioxidant effects were chosen for further study. The ability of compounds to modulate the expression of antioxidant genes (CAT, GPx, SODs, and Nrf2) was determined in SH-SY5Y cells, and the simplified derivatives 2 and 3 were found to be the most effective. The anti-neuroinflammatory properties of all derivatives were assessed in BV2 microglial cells activated with lipopolysaccharide (LPS). Several derivatives decreased the release of cytokines (Il-1β, IL-6, GM-CSF, and TNF-α) and other damaging molecules (ROS, NO) and also regulated the translocation of Nrf2 and NFκB, and reduced p38 activation. These protective effects were confirmed in a trans-well coculture with BV2 and SH-SY5Y cells and several derivatives increased SH-SY5Y survival. This present work demonstrates the neuroprotective properties of gracilin A derivatives, making them promising candidate drugs for AD. Particularly, derivatives 2 and 3 showed the greatest potential as lead compounds for further developmentThe research leading to these results has received funding fromthe following FEDER cofunded-grants. From Consellería de Cultura, Educación e Ordenación Universitaria Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2, ITC-20161072. From European Union POCTEP 0161-Nanoeaters−1-E-1, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018 and H2020 778069-EMERTOX. Support from NIH (R37GM052964 to D.R.) and the Robert A. Welch Foundation (AA-1280 to D.R.) is also gratefully acknowledged.This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical neuroscience, copyright © 2019 American Chemical Society, after peer review and technical editing by the publisher.S

Extractive Dearomatization of Naphthalane Oil Fraction with Ionic Liquid and -N-Methyl-2-Pyrrolidone

In the article are given an analysis of the results of researches carried out for the purpose of selective treatment of the Naphthalane oil fraction boiling at 260-3400C with ionic liquid (IL) -morfolinphormiate synthesized on the basis formic acid + morpholine and - N-methyl-2-pyrrolidon (N-MP) and  as an extractant. The aim is to remove poisonous components -  sulfur compounds and toxic carcinogenic polynuclear aromatic hydrocarbons in order to improve therapeutic properties of Naphthalane oil cut. For this purpose we have used extraction method. On the basis of the conducted researches the role of -N-methyl-2-pyrrolidone and IL-morpholinephormiatee in extraction conditions have been determined in selective treatment of Nafthalan oil, according to the results of spectral analysis residual amount of aromatic hydrocarbons decreased from 18.5% wt accordance to 2%, 1.5%. As well as the amount of sulphur decreased from 0.0354% to 0.010%,  0.011% and 0.019%.In the next stage the treated raffinates with N-methyl-2-pyrrolidone has been purified on silica. In a result amount of aromatic hydrocarbons drastically decrease to be 0.07% and 0.02%. As a result we aquire transparency and at the same time the percentage amount of aromatic hydrocarbons drastically decreased from 2% to 0,07%, 1.5%, to 0.02%. Raffinates obtained in a 2-4 stage dearomatization with N-MP and IL. Raffinate are measured on NMR, UV and IR spectral analysis

Simplified immunosuppressive and neuroprotective agents based on gracilin A

The architecture and bioactivity of natural products frequently serve as embarkation points for the exploration of biologically relevant chemical space. Total synthesis followed by derivative synthesis has historically enabled a deeper understanding of structure–activity relationships. However, synthetic strategies towards a natural product are not always guided by hypotheses regarding the structural features required for bioactivity. Here, we report an approach to natural product total synthesis that we term ‘pharmacophore-directed retrosynthesis’. A hypothesized, pharmacophore of a natural product is selected as an early synthetic target and this dictates the retrosynthetic analysis. In an ideal application, sequential increases in the structural complexity of this minimal structure enable development of a structure–activity relationship profile throughout the course of the total synthesis effort. This approach enables the identification of simpler congeners retaining bioactivity at a much earlier stage of a synthetic effort, as demonstrated here for the spongiane diterpenoid, gracilin A, leading to simplified derivatives with potent neuroprotective and immunosuppressive activityThe authors acknowledge support from the NIH (R37 GM052964 to D.R.), NSF (CHE1800411, to D.R.) the Robert A. Welch Foundation (AA-1280 to D.R.), FEDER co-funded grants from CONSELLERIA DE Cultura, EDUCACION e ordenación Universitaria Xunta de Galicia (2017 GRC GI-1682, ED431C 2017/01), CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad (AGL2014- 58210-R, AGL2016-78728-R, AEI/FEDER, UE) (to L.M.B.), ISCIII/PI1/01830 (to A.A.) and RTC-2016-5507-2 and ITC-20161072, from EU POCTEP 0161-Nanoeaters-1-E-1, Interreg AlertoxNet EAPA-317-2016 and H2020 778069-EMERTOX (to L.M.B.) and from the European Union’s Seventh Framework Programme managed by the Research Executive Agency (FP7/2007-2013 under grant agreement 312184 PHARMASEA to L.M.B. and M.J.). N. Bhuvanesh and J. Reibenspies (Center for X-ray Analysis, TAMU) secured X-ray data and W. Russell (Laboratory for Biological Mass Spectrometry, TAMU) provided mass data. Correspondence and requests for materials should be directed to D. Romo (chemistry) and L. Botana (biology).S

ISSR Analysis of Variability of Cultivated Form and Varieties of Pomegranate (Punica granatum L.) from Azerbaijan

The article presents the results of a study of genetic polymorphism for the first time carried out on pomegranate varieties and forms of Azerbaijan origin using molecular markers. In total, 102 PCR fragments were identified, of which 80 were polymorphic. The high level of polymorphism (75.5%) and the rich genetic diversity were identified among the studied pomegranate collection. As a result of data analysis and on the basis of the values of the basic parameters (PIC, EMR, MI, RP, MRP) determining informativeness of markers, all 14 ISSR primers were suitable for genotyping pomegranate accessions. The most effective markers (UBC808, UBC811, UBC834, and UBC840) were identified among the set of primers tested. A dendrogram was constructed on the basis of the data obtained, which made it possible to group genotypes into 16 major clusters. The genetic similarity index ranged from 0.032 to 0.94. The study of the genetic relationship of different pomegranate varieties confirms the effectiveness of the ISSR method, which makes it possible to determine the level of genetic diversity, as well as to establish the relationship among the studied pomegranate accessions

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population