Enantioselective synthesis of α-(3-pyrrolyl)methanamines with an aza-tetrasubstituted center under metal-free conditions.

Construction of a chiral methanamine unit at the C3 position of pyrrole is highly desirable; nevertheless, it remains challenging due to its intrinsic electronic properties. Herein, we present an operationally straightforward and direct asymmetric approach for accessing α-(3-pyrrolyl)methanamines under benign organocatalytic conditions for the first time. The one-pot transformation proceeds smoothly through an amine-catalyzed direct Mannich reaction of succinaldehyde with various -cyclic imines, followed by a Paal-Knorr cyclization with a primary amine.

Organocatalytic Asymmetric Construction of 2,6-Diazabicyclo-[2.2.2]octanes by Harnessing the Potential of an 3-Oxindolium Ion Intermediate.

Due to its structural complexity and intrinsic sensitivity of bridged aminal junction, 2,6-diazabicyclo[2.2.2]octane (2,6-DABCO) has remained a highly desirable target in synthetic chemistry.

Identification of antiviral phytochemicals from cranberry as potential inhibitors of SARS-CoV-2 main protease (M).

Cranberry phytochemicals are known to possess antiviral activities. In the current study, we explored the therapeutic potential of cranberry against SARS-CoV-2 by targeting its main protease (M) enzyme. Firstly, phytochemicals of cranberry origin were identified from three independent databases.

Electrochemical Synthesis of 2-Aryl-3-(2-aminoaryl)quinoxalines via Oxidative Dearomatization/Ring-Opening/Cyclization Cascade Sequence of 2-Arylindoles with 1,2-Diaminoarenes.

A straightforward method has been developed to synthesize 2-aryl-3-(2-aminoaryl) quinoxalines from 2-arylindoles and 1,2-diaminoarenes under mild electrochemical conditions. The reaction proceeds through in situ generations of 2-arylindole-3-ones under electrochemical oxidative dearomatization of 2-arylindoles, followed by a ring opening-cyclization sequence with 1,2-diaminoarenes. A series of 2-aryl-3-(2-aminoaryl) quinoxalines have been prepared with moderate to good yields (up to 75%).

Electrochemical Oxidative Addition of Nucleophiles on 2-Arylindoles: Synthesis of C2-Heteroquaternary Indolin-3-ones.

An electrochemical method has been developed to synthesize 2,2-disubstituted indolin-3-ones under mild conditions. A series of nucleophiles have been added to the 2-arylindole-3-ones, generated in situ under metal-free electrochemical oxidative dearomatization of 2-arylindoles, to afford 2,2-disubstituted 3-carbonyl indoles with heteroquaternary centers in 57-79% yields.

Enantioselective Direct Synthesis of C3-Hydroxyalkylated Pyrrole via an Amine-Catalyzed Aldol/Paal-Knorr Reaction Sequence.

Creating functionality with chirality at position C3 of pyrrole is challenging. An operationally simple organocatalytic method has been developed to generate functionality with a chiral tertiary/quaternary stereocenter at position C3 of pyrrole. The process proceeds through an amine-catalyzed direct aldol reaction of succinaldehyde with various acceptor carbonyls, followed by a Paal-Knorr reaction with a primary amine in the same pot.

PIFA-promoted intramolecular oxidative cyclization of pyrrolo- and indolo[1,2-]quinoxalino-appended porphyrins: an efficient synthesis of ,β-pyrrolo- and indolo[1,2-]quinoxalino-fused porphyrins.

We have developed an efficient protocol for the synthesis of ,β-pyrrolo- and indolo[1,2-]quinoxalino-fused porphyrin systems 7-9 by PIFA-promoted intramolecular oxidative cyclization of easily accessible -pyrrolo- and indolo[1,2-]quinoxalino-appended porphyrins 6a-j. The absorption spectra of ,β-pyrrolo- and indolo[1,2-]quinoxalino-fused porphyrins 7-9 displayed bathochromic shifted (100-150 nm) and broadened Soret bands and Q bands in addition to intense band near IR region. The indolo[1,2-]quinoxalino-fused porphyrin 9bZn with lower fluorescence quantum yield (0.

Catalyst-free direct regiospecific multicomponent synthesis of C3-functionalized pyrroles.

An operationally simple catalyst-free protocol for the direct regiospecific synthesis of β-(C3)-substituted pyrroles has been developed. The enamine intermediate, generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal-Knorr reaction in a direct multicomponent "just-mix" fashion to furnish pyrroles with overall good yields. Several C3-substituted -alkyl/aryl/H pyrroles have been produced under open-flask conditions with high atom economy and avoiding protection-deprotection chemistry.

Two-pot synthesis and photophysical studies of 1,6-disubstituted 5-aza-indoles from succinaldehyde and -aryl propargylic-imines.

A two-pot synthesis of 5-aza-indoles has been developed from aqueous succinaldehyde and -aryl propargylic-imines. This overall protocol involves: (i) the metal-free [3 + 2] annulation of aqueous succinaldehyde and -aryl propargylic-imines to access 2-alkynyl-pyrrole-3-aldehydes and (ii) Ag-catalyzed 6--cyclization to obtain substituted 5-aza-indoles in the second pot. The 5-aza-indoles showed engaging photophysical activities, and the practicality of this pot-economic gram-scale synthesis has been demonstrated.

Asymmetric Synthesis of Bridged -Heterocycles with Tertiary Carbon Center through Barbas Dienamine-Catalysis: Scope and Applications.

A direct aza-Diels-Alder reaction between 2-aryl-3-indolin-3-ones and cyclic-enones has been developed to access chiral indolin-3-one fused polycyclic bridged compounds. This method proceeds via proline-catalyzed Barbas-dienamine intermediate formation from various cyclic-enones such as 2-cyclopenten-1-one, 2-cyclohexene-1-one, and 2-cycloheptene-1-one, followed by a reaction with 2-aryl-3-indol-3-ones. Several indolin-3-ones fusing [2.

and assays reveal potential inhibitors against 3CL main protease of SARS-CoV-2.

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not showing any sign of slowing down even after the ongoing efforts of vaccination. The threats of new strains are concerning, as some of them are more infectious than the original one. A therapeutic against the disease is, therefore, of urgent need.

Modeling rarefied gas-solid surface interactions for Couette flow with different wall temperatures using an unsupervised machine learning technique.

In rarefied gas flows, discontinuity phenomena such as velocity slip and temperature jump commonly appear in the gas layer adjacent to a solid boundary. Due to the physical complexity of the interactions at the gas-solid interface, particularly in the case of systems with local nonequilibrium state, boundary models with limited number of parameters cannot completely describe the reflection of gas molecules at the boundary. In this work, the Gaussian mixture (GM) model, which is an unsupervised machine learning technique, is employed to construct a statistical gas-solid surface scattering model based on the collisional data obtained from molecular dynamics (MD) simulations.

Peptide inhibitors against SARS-CoV-2 2'-O-methyltransferase involved in RNA capping: A computational approach.

The COVID-19 pandemic is still evolving and is caused by SARS-CoV-2. The 2'-O-methyltransferase (nsp16) enzyme is crucial for maintaining the stability of viral RNA for effective translation of viral proteins and its life cycle. Another protein, nsp10, is important for enzymatic activity of nsp16.

Direct catalytic synthesis of β-(C3)-substituted pyrroles: a complementary addition to the Paal-Knorr reaction.

The synthesis of β-(C3)-functionalized pyrroles is a challenging task and requires a multistep protocol. An operationally simple direct catalytic synthesis of β-substituted pyrroles has been developed. This one-pot multicomponent method combined aqueous succinaldehyde as 1,4-dicarbonyl, primary amines, and isatins to access hydroxyl-oxindole β-tethered pyrroles.

Direct Amine-Catalyzed Enantioselective Synthesis of Pentacyclic Dibenzo[,][1,4]oxazepine/Thiazepine-Fused Isoquinuclidines along with DFT Calculations.

A direct protocol for the asymmetric synthesis of dibenzoxazepine/thiazepine-fused [2.2.2] isoquinuclidines is developed.

Sequential multicomponent site-selective synthesis of 4-iodo and 5-iodopyrrole-3-carboxaldehydes from a common set of starting materials by tuning the conditions.

A simple and straightforward method for the synthesis of 4-iodo and 5-iodopyrrole-3-carboxaldehydes is developed from a common set of starting materials by tuning the reaction conditions. This sequential multicomponent protocol involves I-mediated regioselective C4-iodination and aromatization of intermediate dihydropyrrole, generated through proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and imines, to access 4-iodopyrroles. While aerobic oxidative aromatization of dihydropyrrole to pyrrole followed by NIS-mediated regioselective iodination furnished 5-iodopyrroles in a two-pot fashion.

Enantio- and Diastereoselective Two-Pot Synthesis of Isoquinuclidines from Glutaraldehyde and -Aryl Imines with DFT Calculations.

A pot-economic method for the enantio- and diastereoselective synthesis of a [2.2.2] azabicyclic isoquinuclidine system is developed.