Anti Products Research Articles

Geometrical Optimization and Natural Bond Orbital Analysis of Relevant Structures in the Diastereoselective Cuprate Conjugate Addition Reaction of α,β-Unsaturated Lactams using Density Functional Theory

In this study, density functional theory calculations at the wB97XD/Def2TZVPP level were performed to analyze the mechanism underlying the cuprate conjugate addition reaction of α,β-unsaturated lactams. The calculation results were well-aligned with those obtained experimentally–the keto-aminal and aldo-aminal, i.e. 2 and 1a, yield the syn- and anti-products, respectively. The diastereoselectivity reversal originates from the small differences in the structure of the reactants. The pyramidalization and C7N3C2 angle between the aminal carbon, nitrogen and carbonyl carbon are large in 2. The dihedral angle of the aminal oxygen, aminal carbon, nitrogen and carbonyl carbon, O8C7N3C2, is closer to 180º in 2 than in 1a. The NBO analysis revealed string interactions between the lone pair of N3 and carbonyl π*(O1–C2) bond. These results validate the assumption—the planarity around nitrogen in molecule 2 increases the nucleophilicity of the carbonyl oxygen, thereby driving the reaction between molecule 2 and trimethylsilyl chloride (TMSCl), which yields a siloxyiminium cation 5b and this 5b propels the syn addition of dimethylcuprate, leading to the formation of complex 7. The π(C5–C6) (HOMO) and π*(C2–N3) (LUMO) interactions in the siloxyiminium cation explain the increased C5–C6 double bond electrophilicity. The aldo-aminal 1a directly reacts with dimethylcuprate under steric control and yields the anti complex 6a, whose π character is stronger than that of the syn complex 7 and this weak π characteristics of 7 increases its stability to compensate for the trimethylsilyl disturbance. The bicyclic α,β-unsaturated lactam 8 does not contain aminal oxygen and thus remains unreactive during the cuprate conjugate addition reaction. Moreover, its pyramidalization is higher than that of the keto-aminal 2 and its dihedral angle of C8C7N3C2 is closer to 180º. Finally, a thermodynamic anti product is obtained, which is more stable than the syn- product because of less torsional strain.

Photomechanochemical control over stereoselectivity in the [2+ 2] photodimerization of acenaphthylene.

Tuning solubility and mechanical activation alters the stereoselectivity of the [2 + 2] photochemical cycloaddition of acenaphthylene. Photomechanochemical conditions produce the syn cyclobutane, whereas the solid-state reaction in the absence of mechanical activation provides the anti. When the photochemical dimerization occurs in a solubilizing organic solvent, there is no selectivity. Dimerization in H2O, in which acenaphthylene is insoluble, provides the anti product. DFT calculations reveal that insoluble and solid-state reactions proceed via a covalently bonded excimer, which drives anti selectivity. Alternatively, the noncovalently bound syn conformer is more mechanosusceptible than the anti, meaning it experiences greater destabilization, thereby producing the syn product under photomechanochemical conditions. Cyclobutanes are important components of biologically active natural products and organic materials, and we demonstrate stereoselective methods for obtaining syn or anti cyclobutanes under mild conditions and without organic solvents. With this work, we validate photomechanochemistry as a viable new direction for the preparation of complex organic scaffolds.

Selective photodimerization of acenaphthylene in polymersome nanoreactors.

PEG-b-PLA polymersomes are used as nanoreactors for the photodimerization of acenaphthylene (ACE), increasing reaction rate significantly. The reaction steered towards almost exclusive formation of anti product (94 : 6). This selectivity is remarkable, as other known systems commonly mediate formation of the syn product.

Diastereoselective Substitution Reactions of Acyclic β-Alkoxy Acetals via Electrostatically Stabilized Oxocarbenium Ion Intermediates.

Substitution reactions of acyclic β-alkoxy acetals proceeded with generally high diastereoselectivities (>90:10) to form the anti product. Mechanistic experiments supplemented with computational studies suggest that, upon activation of the acetal, the resulting oxocarbenium ion is electrostatically stabilized by the β-alkoxy group. This stabilization defines the conformation of the reactive intermediate, which can be attacked preferentially from the more exposed face, leading to the observed products.

Biometric Vehicle Access And Ignition System Using Fingerprint Recognition

As variety of urban cars is growing very increasingly with the economy, and considering the individuals are becoming a lot about vehicle thievery which creates larger market for anti vehicle theft products. After that A lots of anti theft devices are being installed in vehicle but result is still unsatisfactory. Since every kind of devices has its own drawbacks therefore ,enhanced system has been proposed in this paper to ensure the vehicle safety and track of vehicle in the event of theft of vehicle. In this system we are using fingerprint based authentication to ignite the engine in addition to key mechanism. In this system we are using a Fingerprint Module (R307),Dc motor ,Motor Driver IC, CP-2102 USB to TTL Module, A MC ATMega 328P on a Self Made ARD. Uno board. A Guiding Wire for guiding the Structure, and Software IDE (Arduino IDE) for Programming the MC. The Heart of the entire System is MC ATMega 328P which is completely responsible for entire operation of Biometric authentication access to owner of vehicle.

Antibodies production in gender groups for surviving COVID-19.

Objectives: A pilot study was executed in the month of June- July 2020 in Qazi Hussain Ahmed Medical complex Nowshera with aim to determine the gender protective role in term of production of neutralizing Anti SARS-COV-2 antibodies. Material and methods: A total of 39 COVID-19 patients who recovered from COVID-19 were selected. Their antibodies cut off values were measured by electro-chemiluminescence immunoassay using Roche Cobas E411 Chemistry Analyzer for which commercial kits of Roche diagnostics were used as per the instructions of the manufacturer. Results: A statistically significant difference in mean post infection antibodies level was observed with higher cut off values in patient who had symptoms at time of being reported positive by PCR as compared to patient who were asymptomatic (p-value:0.04). Using Kaplan Meir it was predicted that in female gender, the probability of survival is 100% at cut off antibodies levels of 50, While a vertical drop up to less than 40% of probability of survival was predicted in male gender even at higher antibodies levels of >100, that supports the prediction of production of higher levels of antibodies in female gender in early infections. Conclusion: The female gender produces higher titer of antibodies in early infections to confer immunity in COVID-19.

Exploring Free Energy Profiles of Enantioselective Organocatalytic Aldol Reactions under Full Solvent Influence.

We present a computational study on the enantioselectivity of organocatalytic proline-catalyzed aldol reactions between aldehydes in dimethylformamide (DMF). To explore the free energy surface of the reaction, we apply two-dimensional metadynamics on top of ab initio molecular dynamics (AIMD) simulations with explicit solvent description on the DFT level of theory. We avoid unwanted side reactions by utilizing our newly developed hybrid AIMD (HyAIMD) simulation scheme, which adds a simple force field to the AIMD simulation to prevent unwanted bond breaking and formation. Our condensed phase simulation results are able to nicely reproduce the experimental findings, including the main stereoisomer that is formed, and give a correct qualitative prediction of the change in syn:anti product ratio with different substituents. Furthermore, we give a microscopic explanation for the selectivity. We show that both the explicit description of the solvent and the inclusion of entropic effects are vital to a good outcome—metadynamics simulations in vacuum and static nudged elastic band (NEB) calculations yield significantly worse predictions when compared to the experiment. The approach described here can be applied to a plethora of other enantioselective or organocatalytic reactions, enabling us to tune the catalyst or determine the solvent with the highest stereoselectivity.

Exploring the Secrets of the Corona Virus: Gender Competition in Antibodies Production to Combat COVID-19

We did a pilot study in the month of July 2020 in Qazi Hussain Ahmed Medical complex Nowshera with aim to determine the gender protective role in term of production of neutralizing Anti SARS-COV-2 antibodies. A total of 39 COVID-19 patients with recovery were selected and their antibodies cut off values were measured by electro-chemiluminescence immunoassay using Roche Cobas E411 Chemistry Analyzer for which commercial kits of Roche diagnostics were used as per the instructions of the manufacturer. It was observed that Difference in mean post infection antibodies level was statistically significant with higher cut off values in patient who had symptoms at time of being reported positive by PCR as compared to patient who were asymptomatic (p-value:0.04). We predicted using Kaplan Meir that female gender the probability of survival as 70% in with cut off values of 100, while a vertical drop up to less than 20% probability of survival was predicted in male gender. Hence female gender produces higher level of antibodies in early infections to confer immunity in COVID-19.

Organocatalysed conjugate addition reactions of aldehydes to nitroolefins with anti selectivity

Catalytic reactions that enable access to different diastereoisomers are important but often difficult to achieve. One long-standing unsolved challenge is the anti-selective conjugate addition reaction between aldehydes and nitroolefins. This organocatalytic transformation is a versatile method for the synthesis of γ-nitroaldehydes and downstream compounds such as pyrrolidines and γ-butyrolactams, which are key moieties in bioactive molecules. Numerous amine catalysts have been developed for this transformation, but all provide syn-configured products. Here, we present a tripeptide as a general catalyst for the synthesis of anti-configured γ-nitroaldehydes. Key to the anti selectivity is the installation of substituents at Cδ of the reactive pyrrolidine of proline to enable the formation of s-cis enamine intermediates. The peptidic catalyst converts different aldehyde and nitroolefin combinations into the products in high yields and stereoselectivities. Conformational and mechanistic studies revealed a Curtin–Hammett scenario for the catalytic system. The strategy provides long-sought-after access to anti-configured γ-nitroaldehydes and a guide for reversing the diastereoselectivity of amine-based organocatalysts. The organocatalysed addition of aldehydes to nitroolefins is an extremely well-studied reaction that almost exclusively provides the syn-configured products. Here a general method to reverse the diastereoselectivity is reported, whereby a tripeptide catalyst consistently provides the anti product with high selectivity.

Selenophosphoramide-catalyzed diamination and oxyamination of alkenes.

A new selenophosphoramide-catalyzed diamination of terminal- and trans-1,2-disubstituted olefins is presented. Key to the success of this transformation was the introduction of a fluoride scavenger, trimethylsilyl trifluoromethanesulfonate (TMSOTf), to prevent a competitive syn-elimination pathway, as was the use of a phosphoramide ligand on selenium to promote the desired substitution reaction. A screen of catalysts revealed that more electron-rich phosphine ligands resulted in higher yields of the desired product, with selenophosphoramides giving the optimal results. A broad range of substrates and functional groups were tolerated and yields were generally good to excellent. For (E)-1,2-disubstituted olefins, diastereoselectivities were always high, giving exclusively anti products. The conditions were also applied to substrates bearing internal nucleophiles such as esters and carbonates, giving rise to 1,2-aminoesters and cyclic carbonates, respectively.

Theoretical Study of Diastereoselective NHC-Catalyzed Cross-Benzoin Reactions between Furfural and N-Boc-Protected α-Amino Aldehydes.

The mechanism and origins of syn and anti selectivity of cross-benzoin reactions between furfural and α-amino aldehydes, catalyzed by a triazolium-based NHC, were investigated using density functional theory calculations. N-Boc-α-amino aldehydes were found to react with anti selectivity, while N-Bn-N-Boc-α-amino aldehydes react with syn selectivity. We find that the anti product is more thermodynamically favored than the syn product for reactions with N-Boc-α-amino aldehydes, and that the formation of the syn product for reactions involving N-Bn-N-Boc-α-amino aldehydes is kinetically favored. The switch in selectivity is a result of an intramolecular hydrogen bond in the N-Boc-α-amino aldehyde, whereas switching to N-Bn-N-Boc-α-amine removes the hydrogen bond. The steric and electronic interactions in the transition state are rationalized by a Felkin-Anh model.

Acyclic Stereocontrol in the Additions of Nucleophilic Alkenes to α-Chiral N-Sulfonyl Imines.

Diastereoselective Lewis acid-mediated additions of nucleophilic alkenes to N-sulfonyl imines are reported. The canonical polar Felkin-Anh model describing additions to carbonyls does not adequately describe analogous additions to N-sulfonyl imines. Herein, we describe the development of conditions to produce both syn and anti products with high diastereoselectivity and good yields. A stereoelectronic model consistent with experimental outcomes is also proposed.

Role of NIB in connecting science to patients by assuring safe and quality anti diabetic products

In India burden of diabetes is increasing and expected to cross the 100 million mark by 2030. Therefore, the development of national policies for the prevention, treatment, and care of diabetes in line with the sustainable development of health care systems is the need of the hour. National Institute of Biologicals (NIB) responsibly assures and reviews the quality of Biological products to the end users by weeding out “Not-of-Standard-Quality” Biological Medicines from reaching Indian market, thereby safeguarding the Public Health by testing at our state-of-art-laboratory. NIB receives samples from various sources such as State Port offices, Central Drug Standard Control Organization (CDSCO), Stakeholders of biotherapeutic manufacturers, legal & global tender samples. They are tested by pharmacopoeial methods or manufacturer’s method for Key Quality Attributes (KQA). The heterogeneity of products involves human recombinant biotherapeutic Insulin, Insulin Analogues, and Peptides of nearly 20 different types eg. Biphasic Insulin, Glargine, Aspart, Exenatide, Liraglutide, etc. which have their global presence for the antidiabetic patient care. Testing for quality attributes such as Identification, Potency, Purity, Stability, Related Impurity and Safety parameters along with the physiochemical test is carried out to ensure the safety, quality, and effectiveness of the product. In addition, reference standards are also being developed at NIB which serves as the measurement standards and complements the written standards in India pharmacopeia. All the testing is carried out strictly adhering to the timelines so that the quality product is delivered to meet the ever-growing public health challenge
 NIB maintains quality systems of ISO 17025 standards for continuous improvement, function as Central Drugs Laboratory(CDL). It focuses on a continuous supply of lifesaving biotherapeutics to ensure the success of the Non-Communicable Disease (NCD) programme for Diabetes.

Analytical Methods: Electrochemical azido-selenenylation of some olefins by cyclic voltammetry and controlled-potential coulometry

Electrochemical azido-phenylselenenylation of some olefins was studied with the oxidation of diphenyl diselenide in the presence of some olefins and sodium azide in dimethyl formamide containing tetra butyl ammonium perchlorate as supporting electrolyte in an H-type cell. The electrochemical oxidation of the mixture of (PhSe)2, olefins, and NaN3 was studied by cyclic voltammetry and controlled-potential coulometry. Anti product can be obtained with Markovnikov orientation. This product was characterized .by 1H, 13C NMR, and IR spectroscopy.

Enantioselective and Diastereoselective Ir-Catalyzed Hydrogenation of α-Substituted β-Ketoesters via Dynamic Kinetic Resolution.

An iridium/f-amphol catalytic system for the enantioselective hydrogenation of α-substituted β-ketoesters via dynamic kinetic resolution is reported. The desired anti products were obtained in high yields (up to 98%) with good diastereoselectivity (up to 96:4 diastereometic ratio (dr)) and excellent enantioselectivity (up to >99% enantiomeric excess (ee)). A catalytic model is proposed to explain the stereoselectivity.

Entrepreneur Capability in Pekalongan City: Issues of Gender, Local Culture and Anti Plagiation Spirit for Creative Community

Pekalongan City is the first creative city in Indonesia to be included in the world creative city list by UNESCO in Craft and Folk Art category. The creativity aspect as the motor of the creative industry in Pekalongan will refer to culture, technology and intellectual property as a strategic driving force in the industry. Another aspect is the issue of gender and entrepreneurial capabilities in line with the needs of the entrepreneur to develop the idea of a product that must always be renewable as a prerequisite of living in the creative economy. The development of two new variables in the creative economy paradigm in the context of entrepreneurial capabilities other than innovative, proactive and risk-taking variables is the anti plagiarism spirit of design and the unique value of the product. The direction of this paper is to know whether there is any influence of gender in its contribution to performance aspect, commitment to cultural preservation, and anti plagiarism spirit and unique product development in order to maintain Pekalongan existence as creative city of UNESCO. This study has a sample of 45 men and 45 women as entrepreneurs and creative industry business in Pekalongan City. The statistical approach using Chi Square analysis with conclusion there is no relationship between gender with the three aspects of research in the form of business performance, cultural commitment and anti plagiarism spirit. In the analysis using Cross Tab, provide description that there is gender equation of way of thinking and strategy of survival and commitment between both capability of entrepreneur of man and woman in Pekalongan.

Straightforward and Stereoselective Synthesis of α,β‐Diamino Acid Derivatives by Means of an Organocatalyzed Decarboxylative Mannich Reaction

A rapid and convenient method has been developed for the stereoselective synthesis of α,β‐diamino acid derivatives from amido‐substituted malonic acid half oxyesters (MAHOs) and imines. The anti products were obtained with a diastereomeric ratio up to 99:1 by using a decarboxylative Mannich reaction catalyzed by commercially available 1,4‐diazabicyclo[2.2.2] octane (DABCO).

Nanoemulsion Containing SangYod Rice Bran Oil and Thanakha Extracts: <i>In Vitro </i>Antioxidant and Irritation Assessments

Nanoemulsions are well characterized in a promising drug delivery system with applications for drug and cosmetic. Traditionally and cosmetic industries use Rice bran oil and Hesperethusa crenulata or Thanakha bark aqueous extract in sunscreen formulations, anti ageing products and in treatments for skin diseases. The aim of this study was to produce the nanoemulsion and to evaluate their physical stability, irritation potential. In vitro study, the total phenolic contents and total antioxidant capacity of SangYod Rice bran oil (SRBO) were 1130.44 ± 53.55 mg GAE/mg and 25.94±4.69 mmol TEAC/mg and Thanakha were 3.85±0.23 mg GAE/gdw and 19.87 ± 2.59 mmol TEAC/gdw, respectively. The nanoemulsion containing SRBO and Thanakha, oil in water, was produced using low-pressure homogenizer and ultrasonicator techniques and the particle size was 167.03±1.75 nm. The stability of nanoemulsion represented no significant change on pH and particle size after day 0, 5, 11, 14 and over 12 month at temperature 4, 25 and 40 °C. Moreover, it’s also showed no irritation on HET–CAM test, a basic test for embryotoxicity, systemic toxicity and immunopathology. Conclusion, these results suggested that the nanoemulsion containing SRBO and Thanakha may serve as potential vehicles for improved transdermal delivery antioxidant compound and no irritation.

First anti‐Selective Direct Michael Addition of α‐Alkoxy Ketones to Enones by Cooperative Catalysis of Samarium(III) Trifluoromethanesulfonate and Tributyltin Methoxide

A new highly anti‐diastereoselective Michael addition of α‐alkoxy ketones to α,β‐unsaturated ketones was achieved. This method features a dual‐catalyst protocol that combines samarium(III) trifluoromethanesulfonate and Bu3SnOMe. The combination of these two catalysts effectively allowed the generation of enolate species from α‐alkoxy ketones and produced Michael adducts in high yields with high anti diastereoselectivity. A variety of enones and α‐alkoxy ketones were applied to this system to give the anti products. One‐pot domino Michael/aldol reactions effectively afforded cyclic enones with a defined configuration.

Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8-Dichloroanthracene and Acrolein.

A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs) favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product.