Accessing Pyridines via a Nitrene Internalization Process.

Pyridines are valuable pharmacophores, and their access via direct and selective transmutation of carbon atom with desired nitrogen could become crucial in drug discovery processes. However, only scarce examples can be found when it comes C-to-N-transmutation reactions of aromatics that could lead to the facile synthesis of pyridines or other azaarenes. In this context, Levin and co-workers recently disclosed a process leading to pyridines from the corresponding aryl azides via the regioselective nitrene internalization process. Notably, the transformation did not lead to any further modification of the rest of the aromatic skeleton. This innovative work enabled selectively accessing various pyridine derivatives through direct nitrogen scan operations on benzene derivatives, which were otherwise not feasible.

Asymmetric synthesis of spirocyclic isobenzofuranones via a squaramide-catalysed sulfa-Michael desymmetrisation reaction.

Enantioselective synthesis of spirocyclohexenone isobenzofuranones has been achieved through an organocatalysed sulfa-Michael desymmetrisation reaction. A cinchona-derived squaramide effectively promotes the desymmetrisation of spirocyclic 2,5-cyclohexadienone isobenzofuranones via the controlled addition of various aryl thiols to generate two vicinal stereocenters with perfect diastereoselectivities and up to very good enantioselectivities.

In vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity of Murraya koenigii leaf extract intercedes ZnO nanoparticles.

Nanotechnology is an emerging field with tremendous potential and usage of medicinal plants and green preparation of nanoparticles (NPs) is one of the widely explored areas. These have been shown to be effective against different biological activities such as diabetes mellitus, cancer, antioxidant, antimicrobial, etc. The current studies focus on the green synthesis of zinc NPs (ZnO NPs) from aqueous leaf extract of Murraya koenigii (MK). The synthesized Murraya koeingii zinc oxide NPs (MK ZnO NPs) were characterized using UV-visible spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive spectrum (EDS) and cyclic voltammetry (CV). The synthesized MK ZnO NPs were evaluated for their in vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity. They demonstrated significant antidiabetic and cytotoxic activity, as well as moderate free-radical scavenging and antibacterial activity.

Comparative analysis of discharge and sediment flux from two contiguous glacierized basins of Central Himalaya, India.

In the present study, suspended sediment load (SSL), sediment yield and erosion rates in Pindari Glacier basin (PGB) and Kafni Glacier basin (KGB) have been estimated using daily discharge and suspended sediment concentration (SSC) data for three ablation seasons (2017-2019). For this, one meteorological observatory and two gauging sites have been established at Dwali (confluence point), and water samples have been collected twice in a day for high flow period (July to September) and daily for lean period (May, June and October). An area-velocity method and stage-discharge relationship has been established to convert water level into discharge (m3 s-1). For estimating SSC (mg/l), collected water samples have been filtered, dried, analysed and confirmed with an automatic suspended solid indicator. Further, SSL, sediment yield and erosion rates have been computed using SSC data. The results reveal that mean annual discharge in PGB (35.06 m3 s-1) has been found approximately 1.7 times higher than KGB (20.47 m3 s-1). The average SSC and SSL in PGB have been observed about 396.07 mg/l and 1928.34 tonnes, and in KGB, it is about 359.67 mg/l and 1040.26 tonnes, respectively. The SSC and SSL have followed the pattern of discharge. A significant correlation of SSC and SSL has been found with discharge in both the glacierized basins (p < 0.01). Interestingly, average annual sediment yield in PGB (3196.53 t/km2/yr) and KGB (3087.23 t/km2/yr) have been found almost identical. Likewise, the erosion rates in PGB and KGB have been witnessed about 1.18 and 1.14 mm/yr, respectively. Sediment yield and erosion rates in PGB and KGB have been found in correspondence with other basins of Central Himalaya. These findings will be beneficial for engineers and water resource managers in the management of water resources and hydropower projects in high-altitude areas and in the planning and designing of water structures (dams, reservoirs etc.) in downstream areas.

Carbene Formation or Reduction of the Diazo Functional Group? An Unexpected Solvent-Dependent Reactivity of Cyclic Diazo Imides.

The control of the reactivity of diazo compounds is commonly achieved by the choice of a suitable catalyst, e.g. via stabilization of singlet carbenes or radical intermediates. Herein, we report on the light-promoted reactivity of cyclic diazo imides with thiols, where the choice of solvent results in two fundamentally different reaction pathways. In dichloromethane (DCM), a carbene is formed initially and engages in a cascade C-H functionalization/thiolation reaction to deliver indane-fused pyrrolidines in good to excellent yields. When switching to acetonitrile solvent, the carbene pathway is shut down and an unusual reduction of the diazo compound occurs under otherwise identical reaction conditions, where the aryl thiol acts as reductant. A combined set of experimental and computational studies was carried out to obtain mechanistic understanding and to support that indane formation proceeds via the insertion of a triplet carbene, while the reduction of diazo imides proceeds via an electron transfer process.

Asymmetric Synthesis of Cyclohexenone-Fused Isochromans via Quinidine-Catalyzed Domino Peroxyhemiacetalization/Oxa-Michael Addition/Desymmetrization Sequence.

A highly enantio- and diastereoselective synthesis of highly functionalized isochromans was achieved through an organocatalyzed domino reaction. Quinidine as the catalyst initiates a peroxyhemiacetalization/oxa-Michael/desymmetrization domino sequence between various 2,5-cyclohexadienone-tethered aryl aldehydes with hydroperoxides to generate the single diastereomers of isochromans appended with a cyclohexenone ring bearing three vicinal stereocenters in good yields and high enantioselectivities under ambient reaction conditions.

Lycopene: a therapeutic strategy against coronavirus disease 19 (COVID- 19).

Lycopene is a group of phytochemicals found in nature, primarily in fruits and vegetables. Lycopene is thought to protect against a variety of diseases attributed to its antioxidant capabilities. Lycopene has anti-inflammatory, anti-cancer, and immunity-boosting qualities, among other biological and pharmacological benefits. COVID-19 (coronavirus disease 19) is an infectious disease caused by the SARS-CoV-2 virus, which has recently emerged as one of the world's leading causes of death. Patients may be asymptomatic or show signs of respiratory, cytokine release syndrome, gastrointestinal, or even multiple organ failure, all of which can lead to death. In COVID-19, inflammation, and cytokine storm are the key pathogenic mechanisms, according to SARS-CoV-2 infection symptoms. ARDS develops in some vulnerable hosts, which is accompanied by an inflammatory "cytokine syndrome" that causes lung damage. Immunological and inflammatory markers were linked to disease severity in mild and severe COVID-19 cases, implying that inflammatory markers, including IL-6, CRP, ESR, and PCT were significantly linked with COVID-19 severity. Patients with severe illness have reduced levels of several immune subsets, including CD4 + T, NK, and CD8 + cells. As a result, lycopene can be commended for bolstering physiological defenses against COVID-19 infections.

Electrochemical Oxidative Coupling Between Benzylic C(sp3)-H and N-H of Secondary Amines: Rapid Synthesis of α-Amino α-Aryl Esters.

An intermolecular electrochemical coupling between the benzylic C(sp3)-H bond and various secondary amines is reported. The electronic behavior of two electronically rich units viz the α-position of α-aryl acetates and amines was engineered electrochemically, thus facilitating their reactivity for the direct access of α-amino esters. A series of acyclic/cyclic secondary amines and α-aryl acetates were tested to furnish the corresponding α-amino esters with high yields (up to 92%) under mild conditions.

Catalytic asymmetric umpolung reactions of imines via 2-azaallyl anion intermediates.

The imine umpolung is a relatively new and interesting strategy, especially in catalytic asymmetric synthesis. A significant development in organo- and transition metal-catalyzed umpolung of imines took place only in the recently concluded decade. A majority of the reports on the asymmetric umpolung of imines involve the initial generation of 2-azaallyl anion intermediates with the chiral catalysts, which serve as a significant driving force for the umpolung addition/substitution reactions. A variety of organocatalysts such as bifunctional cinchona alkaloids including squaramides and thioureas, chiral BINOL derived phosphoric acids, phase transfer catalysts (PTCs), phosphines, and transition metal-complexes of iridium, copper and palladium have been employed to achieve the excellent level of asymmetric induction in such types of umpolung reactions. The asymmetric imine umpolung strategy has been applied successfully to synthesize synthetic amino-acid derivatives and other useful chiral amines, including drugs and potentially bioactive molecules. This review summarizes all the significant recent development in catalytic umpolung reactions of imines involving a 2-azaallyl anion intermediate.

Achieving Molecular Complexity via Stereoselective Multiple Domino Reactions Promoted by a Secondary Amine Organocatalyst.

In the last two decades, organocatalysis has emerged as an intensively investigated and rapidly growing area of research facilitating many known and many new transformations to provide efficient novel entries to complex molecules of high stereochemical purity. The organocatalysts have not only shown their efficiency for catalyzing the reactions in which one bond is formed, but they have also been effectively exploited in various versions of one-pot reactions. Domino reactions are one of the most important classes of one-pot reactions, where the target structure can be obtained in one pot without changing any reaction conditions while each reaction occurs as a consequence of the intermediates generated in previous steps. Owing to the synthetic importance and operational advantages associated with the use of organocatalysts and the development of domino reactions, various asymmetric transformations leading to a complex structure of choice have been explored. The early era of organocatalysis exhibits a limited growth in the development of asymmetric domino reactions with special emphasis on two reactions occurring one after the other. In 2006, our group made a step forward to develop more complex domino reactions catalyzed by a secondary amine organocatalyst, wherein three reactions take place in one pot to provide cyclohexene carbaldehydes bearing four stereogenic centers with excellent stereocontrol. This triggered our interest to develop new organocatalytic domino sequences, especially for multiple domino reactions. After our seminal contribution, domino reactions catalyzed by secondary amine organocatalysts not only became more popular, but they also could be catalyzed by other classes of organocatalysts, such as bifunctional hydrogen bonding catalysts, chiral Brønsted acids, and N-heterocyclic carbenes. The mode of activation in this triple domino reaction relied on the sequential generation of enamine and iminium intermediates using a proline-based chiral secondary amine organocatalyst. By employing this strategy, we have developed several triple domino reactions leading to the formation of carbo- and heterocyclic structures bearing multiple stereogenic centers with excellent levels of stereoselectivities. The applications of the secondary amine organocatalysts have been further extended to more complex quadruple domino sequences. Moreover, these multiple domino sequences have been combined successfully with other transformations in one pot to create densely functionalized polycyclic compounds. This Account gives an overview of our research in the area of organocatalytic asymmetric multiple domino reactions with special emphasis on the secondary amine catalyzed triple and quadruple domino reactions via a sequential generation of enamine and iminium intermediates. The multiple cascade reactions assisted by di- and tri-iminium and -enamine species as well as other types of organocatalysts have been excluded from the scope of this Account.

Journey Heading towards Enantioselective Synthesis Assisted by Organocatalysis.

This personal account summarizes the design of various organocatalysts derived from amino acids and Cinchona alkaloids and their applications in enantioselective carbon-carbon and carbon-nitrogen bond formation reactions. This account begins with the short description of the background of asymmetric organocatalysis. Various types of reactions like aldol reaction, Michael reaction, aza-Henry reaction, Morita-Baylis-Hillman reaction are described in this account.

Asymmetric organocatalytic methods for the synthesis of tetrahydropyrans and their application in total synthesis.

Recent advancement in the area of asymmetric organocatalysis led to the development of new methodologies for the construction of valuable enantiopure molecules, including various heterocycles. As one of the latter class of compounds tetrahydropyrans (THPs) constitute a core structure of a wide array of bioactive natural products. A noticeable growth has been observed in the asymmetric synthesis of THPs using small organic molecules as catalysts. This Tutorial Review describes the organocatalytic methods available to furnish THPs as well as the application of these methodologies in the total synthesis of THP-based natural products.

N-Heterocyclic Carbene Catalysis via Azolium Dienolates: An Efficient Strategy for Remote Enantioselective Functionalizations.

N-heterocyclic carbene (NHC) catalysis has emerged as a powerful strategy in organic synthesis. In recent years a number of reviews have been published on NHC-catalyzed transformations involving Breslow intermediates, acyl azoliums, α,ß-unsaturated acyl azoliums, homoenolate equivalents, and azolium enolates. However, the azolium dienolate intermediates generated by NHCs have been employed in asymmetric synthesis only very recently, especially in cycloadditions dealing with remote functionalization. This Minireview highlights all the developments and the new advances in NHC-catalyzed asymmetric cycloaddition reactions involving azolium dienolate intermediates.

Asymmetric Synthesis of Amino-Bis-Pyrazolone Derivatives via an Organocatalytic Mannich Reaction.

A new series of N-Boc ketimines derived from pyrazolin-5-ones have been used as electrophiles in asymmetric Mannich reactions with pyrazolones. The amino-bis-pyrazolone products are obtained in excellent yields and stereoselectivities by employing a very low loading of 1 mol % of a bifunctional squaramide organocatalyst. Depending on the substitution at position 4 of the pyrazolones, the new protocol allows for the generation of one or two tetrasubstituted stereocenters, including a one-pot version combing the Mannich reaction with a base-mediated halogenation.

Squaramide-Catalyzed Asymmetric aza-Friedel-Crafts/N,O-Acetalization Domino Reactions Between 2-Naphthols and Pyrazolinone Ketimines.

N-Boc ketimines derived from pyrazolin-5-ones were explored to develop an unprecedented domino aza-Friedel-Crafts/N,O-acetalization reaction with 2-naphthols. The novel method requires a catalyst loading of only 0.5 mol % of a bifunctional squaramide catalyst, is scalable to gram amounts, and provides a new series of furanonaphthopyrazolidinone derivatives bearing two vicinal tetra-substituted stereogenic centers in excellent yields (95-98 %) and stereoselectivity (>99:1 d.r. and 97-98 % ee). A different reactivity was observed in the case of 1-naphthols and other electron-rich phenols, which led to the aza-Friedel-Crafts adducts in 70-98 % yield and 47-98 % ee.

N-Heterocyclic Carbene Catalyzed [4+2] Annulation of Enals via a Double Vinylogous Michael Addition: Asymmetric Synthesis of 3,5-Diaryl Cyclohexenones.

A strategy for the N-heterocyclic carbene (NHC) catalyzed asymmetric synthesis of 3,5-diaryl substituted cyclohexenones has been developed via oxidative [4+2] annulation of enals and alkenylisoxazoles. It is the first example of using NHC organocatalysis in a double vinylogous Michael type reaction, a challenging but highly desirable topic. This unprecedented protocol affords good yields as well as high to excellent diastereo- and enantioselectivities.

Identification and expression profiling of DNA methyltransferases during development and stress conditions in Solanaceae.

DNA methyltransferase (DMTase) enzymes contribute to plant development and stress responses by de novo establishment and subsequent maintenance of DNA methylation during replication. However, the molecular mechanism underlying this activity remains obscure, especially in crop species. Using DMTase homolog complement in six Solanaceae species, we demonstrated here that their number remained conserved in Solanum lineage, whereas it was expanded in both pepper and Nicotiana benthamiana. Non-synonymous vs synonymous (Ka/Ks) substitution ratio revealed that most of the Solanaceous DMTase homologs undergo purifying selection. The genomic sequences of tomato DMT homologs in its wild relative, Solanum pennellii, remained highly conserved in their exons and methyltransferase domains. Structure analysis further revealed highly similar folding of DMTase homologs and conservation in the residues participating in protein-protein interaction in Solanum lineage, whereas a considerable diversification was observed of pepper homologs. Transcript profiling of DMTases highlighted both similar and distinct expression patterns of tomato homologs in other species during fruit development and stress responses. Overall, our analysis provides a strong basis for in-depth exploration of both conserved as well as distinct functions of tomato DMTase homologs in other economically important Solanaceae species.

Asymmetric, Three-Component, One-Pot Synthesis of Spiropyrazolones and 2,5-Chromenediones from Aldol Condensation/NHC-Catalyzed Annulation Reactions.

A novel one-pot, three-component diastereo- and enantioselective synthesis of spiropyrazolones has been developed involving the aldol condensation of an enal to generate α,ß-unsaturated pyrazolones, which react with a second equivalent of enal through an N-heterocyclic carbene (NHC)-catalyzed [3+2] annulation. The desired spirocyclopentane pyrazolones are obtained in moderate to good yields and good to excellent stereoselectivities. Alternatively, starting from cyclic 1,3-diketones, 2,5-chromenediones are available through [2+4] annulation.

α,α-Dicyanoolefins: versatile substrates in organocatalytic asymmetric transformations.

α,α-Dicyanoolefins have emerged as versatile reactants, finding use as vinylogous nucleophiles, Michael acceptors and dienophiles in a variety of organic reactions. In the last few years, the reactivity of α,α-dicyanoolefins has been explored in various asymmetric transformations catalyzed by organocatalysts. In this review, we are presenting the recent advances in asymmetric organocatalytic transformations involving α,α-dicyanoolefins.

Catalytic Conia-ene and related reactions.

Since its initial inception, the Conia-ene reaction, known as the intramolecular addition of enols to alkynes or alkenes, has experienced a tremendous development and appealing catalytic protocols have emerged. This review fathoms the underlying mechanistic principles rationalizing how substrate design, substrate activation, and the nature of the catalyst work hand in hand for the efficient synthesis of carbocycles and heterocycles at mild reaction conditions. Nowadays, Conia-ene reactions can be found as part of tandem reactions, and the road for asymmetric versions has already been paved. Based on their broad applicability, Conia-ene reactions have turned into a highly appreciated synthetic tool with impressive examples in natural product synthesis reported in recent years.