Silver-Catalyzed Asymmetric Double Desymmetrization via Vinylogous Michael Addition of Prochiral α,α-Dicyanoalkenes to Cyclopentendiones.

An asymmetric double desymmetrization methodology has been developed for synthesizing densely functionalized chiral cyclopentylcyclohexane scaffolds. We have constructed four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. The methodology has high functional-group tolerance and delivers a broad range of enantioenriched products. This vinylogous Michael addition reaction of prochiral α,α-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst.

Asymmetric Cascade Dearomatization-Cyclization Reaction of Tryptamines with ß,γ-Alkynyl-α-imino Esters: Access to Hexahydropyrrolo[2,3-b]indole-Containing Tetrasubstituted α-Amino Allenoates.

An organocatalytic enantio- and diastereoselective synthesis of hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted α-amino allenoates, exhibiting both axial and central chirality, has been accomplished via cascade dearomatization-cyclization reaction. The γ-addition to ß,γ-alkynyl-α-imino esters provides a library of densely substituted highly enantioenriched allenes in high yields and excellent stereoselectivities. In addition, the scope of this methodology has been extended to tryptophol as well. A scale-up reaction and synthetic transformations of the products were performed to demonstrate the practical usefulness of this approach.

Organocatalytic Asymmetric Cascade Michael-Acyl Transfer Reaction between 2-Fluoro-1,3-diketones and 2-Hydroxynitrostyrenes.

An organocatalytic asymmetric cascade Michael-acyl transfer reaction of 2-hydroxynitrostyrenes and monofluorinated ß-diketones has been developed employing a cooperative catalytic system. A combination of quinine-derived bifunctional squaramide catalyst and achiral hydrogen bond donor cocatalyst was found to be the most effective for this reaction and provided the fluorinated acyl transfer products in high yields with good diastereo- and excellent enantioselectivities. Synthetic transformations have been demonstrated, including the synthesis of functionalized 2,3-dihydrobenzofurans and 1-pyrroline.

Correction: Professor (Dr) Sukh Dev: an iconic scientist with an innate sixth sense who radicalized natural product synthesis & organic chemistry.

Correction for 'Professor (Dr) Sukh Dev: an iconic scientist with an innate sixth sense who radicalized natural product synthesis & organic chemistry' by Harry Kochat et al., Org. Biomol. Chem., 2024, 22, 5466-5469, https://doi.org/10.1039/D4OB90071E.

Enantioselective Dearomative [4+2] Cycloaddition Reaction of 1-Naphthols with In-Situ Generated ortho-Quinone Methides.

We disclose a catalytic, enantioselective dearomative reaction of non-functionalized 1-naphthols, which poses a synthetic challenge to organic chemists because of the relative ease of rearomatization via the elimination of a proton. In this work, the direct dearomatization of non-functionalized 1-naphthols was achieved through a chiral phosphoric acid (CPA) catalyzed enantioselective dearomative [4+2] cycloaddition reaction with in-situ generated ortho-quinone methides (o-QMs). The reported convergent method allows the use of readily available simple 1-naphthols without pre-functionalization, furnishing a variety of naphthopyran derivatives in good yields (up to 96 %) and moderate to excellent enantioselectivities (up to >99 % ee) under mild reaction conditions. The observed regio-, diastereo-, and enantioselectivities are the keys to the success of the current strategy utilizing o-QM as a diene surrogates, in combination with CPA catalysis.

Brønsted Acid Catalyzed Friedel-Crafts Alkylation of Naphthols with In Situ Generated Naphthol-Derived ortho-Quinone Methides: Synthesis of Chiral and Achiral Xanthene Derivatives.

We disclose herein an enantioselective protocol for the Brønsted acid catalyzed addition of naphthols to in situ generated naphthol-derived ortho-quinone methides (o-QMs) followed by intramolecular cyclization, which delivers substituted chiral xanthene derivatives, in a one-pot reaction sequence under mild conditions. This process serves to convert naphthol-derived ortho-hydroxyl benzylic alcohols into reactive naphthol-derived o-QMs using a chiral phosphoric acid (CPA) catalyst. Moreover, it is helpful in controlling the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding followed by intramolecular cyclization. Additionally, for the first time, we observe a Brønsted acid catalyzed C(sp2)-C(sp3) bond cleavage of naphthol-derived ortho-hydroxyl benzylic alcohols for the synthesis of achiral xanthene (sigma plane containing) derivatives in good to excellent yields.

Synthesis of Spiroisoindolinones via Ru(II)-Catalyzed Spiroannulation of N-Acyl Ketimines with Aryl Isocyanates/Isothiocyanates through Aromatic C-H Bond Activation.

Herein, we disclose the first report on Ru(II)-catalyzed amidation/thioamidation of 3-hydroxy-3-arylisoindolinones with isocyanates/isothiocyanates, respectively. The reaction furnishes spiroisoindolinones via sequential C-H functionalization of ortho C-H bond followed by intramolecular cyclization in moderate to high yields (up to 94%). Moreover, the developed strategy is highly atom-economical and site-selective and shows diverse substrate generality. Also, synthesized spiroisoindolinones undergo several chemical transformations.

Chiral Phosphoric Acid-Catalyzed Asymmetric Friedel-Crafts Addition of Indolizine to Cyclic N-Sulfonyl Imine.

A highly efficient chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts addition of indolizine to cyclic N-sulfonyl imine has been established. The newly developed protocol, which probably proceeds via a monoactivation reaction pathway, allows the access of enantioenriched sulfonamide functionalized indolizines with excellent yields (up to 99%) and enantioselectivities (up to 99%). Moreover, the synthetic utility of this protocol has been explored with some chemical transformations.

Organocatalytic Asymmetric Direct Vinylogous Michael Initiated Ring Closure Reaction of 4-Nitroisoxazole Derivatives to 3-Isopropylidene Oxindoles.

Herein, we present the first ever use of 3-isopropylidene oxindoles as electrophiles in vinylogous Michael initiated ring closure reaction (MIRC). Among the various alkylidene oxindoles used in enantioselective spirocyclization reactions, isopropylidene oxindoles are the least explored to date. The competing reactivity of isopropylidene oxindoles (electrophilicity vs nucleophilicity) in the presence of a chiral organocatalyst is controlled by the logical selection of a more reactive nucleophile. The methodology produces a library of densely substituted highly enantioenriched spirocyclopropyl oxindoles with excellent yield and stereoselectivities. Moreover, the first enantioselective synthesis of HIV-1 NNRT inhibitor indicates the importance of our synthesized spiro-cyclopropyl oxindole core.

Kinetic Resolution of Electron-Deficient Bromohydrins via Copper(II)-Catalyzed C-C Bond Cleavage.

Herein, we report a nonenzymatic kinetic resolution (KR) of α,ß-unsaturated ketone-derived bromohydrins (up to s = 211) with N-bromosuccinimide (NBS) in the presence of a chiral Cu(II)-Box catalyst via the C-C bond cleavage of the fast reacting enantiomer. A one-pot synthesis-KR approach of the same has also been realized with excellent enantioselectivities (up to 99% ee). Both protocols are found to be effective for a variety of substrates, leading to enantioenriched bromohydrins. The synthetic utility of this process has been demonstrated by exploring a new strategy to convert the resolved enantiomer to an optically active epoxide.

Study of antibiotics sensitivity pattern and molecular characterization of Staphylococcus aureus isolated from human and animal pyogenic cases.

Staphylococcus aureus has been described as the most common cause of human and animal diseases and has emerged as a superbug due to multidrug resistance. Considering these, a total of 175 samples were collected from pyogenic cases of humans (75) and animals (100), to establish the drug resistance pattern and also for molecular characterization of human and animal isolates. Thermonuclease (nuc) gene amplification was used to confirm all presumptive S. aureus isolates and then, antibiotic sensitivity and slide Coagulase tests were used for phenotypic characterization of isolates. Following that, all the isolates were subjected to PCR amplification to detect the existence of the Methicillin-resistant (mecA) and Coagulase (coa) genes. Lastly, typing was done using the Randomly Amplified Polymorphic DNA-PCR. The overall prevalence of S. aureus in human and animal samples was found to be 39.4%. Drug sensitivity revealed the highest resistance against the ß-lactam antibiotics such as ampicillin (94.8%) and penicillin (90.6%), followed by cephalosporin (cefixime-67.7%) and quinolone (ciprofloxacin-52.1%) group of drugs. The drug sensitivity was the highest against antibiotics like chloramphenicol (95%) followed by gentamicin (90%). Among the 69 S. aureus isolates, the overall presence of MRSA was 40.5% (27.5% and 50% in human and animal isolates, respectively). Total 33 isolates exhibited coa genes amplification of more than one amplicons and variable in size of 250, 450, 800, and 1100 bp. The RAPD typing revealed amplification of five and six different band patterns in humans and animals, respectively, with two common patterns suggesting a common phylogenetic profile.

Asymmetric Synthesis of Spiro-3,3'-cyclopropyl Oxindoles via Vinylogous Michael Initiated Ring Closure Reaction.

A novel organocatalytic cascade approach for the synthesis of spiro-cyclopropyl oxindole derivatives has been developed. The methodology is based on asymmetric vinylogous Michael addition of 4-nitroisoxazole derivatives to N-Boc isatylidene malonates followed by intramolecular alkylation. Its remarkable stereocontrol, wide substrate scope, and scalability highlight this new developed strategy. Moreover, this work represents the first example of vinylogous Michael initiated ring closure (MIRC) reaction for the synthesis of chiral 3,3'-cyclopropyl oxindole.

A Brønsted acid-catalyzed thioacid addition to in situ-generated aldimine for the synthesis of isoindolinones with the N,S-acetal framework.

A facile methodology was demonstrated for the synthesis of isoindolinones containing the N,S-acetal framework by employing a Brønsted acid catalyst with a three-component reaction. The reaction proceeded via the addition of thioacid to in situ-generated aldimine followed by lactamization, which involved the formation of one C-S bond and two C-N bonds under easily controlled and ambient reaction conditions. A variety of substituted isoindolinones were synthesized with up to 99% yields. Furthermore, the importance of this methodology was also justified by a gram-scale synthesis and demonstration of some interesting synthetic transformations.

Enantioselective synthesis of tetrahydrofuran spirooxindoles via domino oxa-Michael/Michael addition reaction using a bifunctional squaramide catalyst.

An enantioselective approach for the synthesis of tetrahydrofuran spirooxindoles via domino oxa-Michael/Michael addition reaction of γ-hydroxyenones to isatylidene malononitriles, using a cinchona derived bifunctional squaramide catalyst has been developed. The methodology is the first success of enantioselective oxa-Michael addition to isatylidene malononitriles. The spiro products were obtained in excellent yields with moderate to good enantio- and diastereoselectivities. Scale-up of the reaction and synthetic transformation of the spiro product into structurally complex molecules have been performed.

Brønsted acid-catalyzed enantioselective addition of 1,3-diones to in situ generated N-acyl ketimines.

A Brønsted acid-catalyzed asymmetric Mannich-type addition of 1,3-diones to cyclic N-acyl ketimines is reported for the synthesis of enantioenriched isoindolinones. Various dicarbonyl-substituted isoindolinones bearing a quaternary carbon stereocenter were synthesized with excellent yields (up to 98%) and moderate to high enantioselectivities (up to 95% ee), and most of them possess a fluorine atom at the reactive center. Furthermore, the synthetic utility of the protocol has been demonstrated by the debenzoylation of the product.

Restoring soil carbon in marginal land of Indian Himalayas: Impact of crop intensification and conservation tillage.

Soil carbon (C) loss is the prime sign of land degradation, and C pools have a great impact on soil quality and climate change mitigation. Hence, a field experiment was conducted for three consecutive years to assess the impact of crop intensification and conservation tillage practices on changes in the C pool at different soil depths of marginal land of the Indian Himalayas. The experiment consisted of two intensified cropping systems viz., CS1-Summer maize (Zea mays L.) -rainy season maize-lentil (Lens esculenta L.) and CS2-Summer maize-rainy season maize-mustard (Brassica juncea (L.) Czern) and five tillage practices viz., No-till (NT); NT + live mulch of cowpea (NT + LMC); reduced tillage (RT); RT + LMC and conventional tillage (CT). Results revealed that CS2 produced significantly higher biomass, C retention efficiency (9.85%), and sequestrated greater C (0.42 Mg ha-1 yr-1) in the soil system than CS1. Of the various tillage practices, RT + LMC registered higher biomass and recycled greater biomass and C than those under other tillage practices. However, the highest soil organic carbon (SOC) content (7.03 g kg-1) and pool (9.62 Mg ha-1) in 0-10 cm depth were observed under NT + LMC. The non-labile C pool size under NT in 0-10 cm and 10-20 cm depths was significantly greater than those under CT. The NT + LMC sequestrated significantly higher SOC (0.57 Mg ha-1 yr-1) than other tillage practices. Thus, the study indicated that the adoption of an intensified maize-based system under RT + LMC or NT + LMC would increase SOC storage and C sequestration in marginal lands of the Indian Himalayas.

A Fatal Case of Acute Disseminated Encephalomyelitis: A Diagnosis to Ponder in Pandemic.

A 40-year-old woman known hypertensive presented with progressive ascending paralysis. MRI T2W and FLAIR screening of the brain demonstrated swelling with altered signal in the visual cervical cord, medulla, and another juxtacortical lesion in the right temporal lobe with possibility of a demyelinating etiology. CSF testing did not identify a direct cerebral infection. High-dose steroids followed by a course of IVIG was administered but with no significant response. In these pandemic times, the patients who present with altered mentation and polyfocal neurological deficits and background history of recent COVID-19 infection or recipient of SARS-CoV-2 vaccine the diagnosis of acute disseminated encephalomyelitis (ADEM) should be considered likely. How to cite this article: Kumar A, Sabharwal P, Gupta P, Singh VK, Rao BK. A Fatal Case of Acute Disseminated Encephalomyelitis: A Diagnosis to Ponder in Pandemic. Indian J Crit Care Med 2022;26(4):518-520.

Cu(I)-Catalyzed asymmetric exo-selective synthesis of substituted pyrrolidines via a 1,3-dipolar cycloaddition reaction.

An (R)-DM-BINAP/Cu(CH3CN)4BF4 complex catalyzed exo-selective asymmetric 1,3-dipolar cycloaddition (1,3-DCA) reaction of imino esters with α,ß-unsaturated pyrazoleamides has been developed. A series of highly functionalized pyrrolidines with multiple stereogenic centers were obtained with good yields and diastereoselectivities and excellent enantioselectivities (up to 99% ee).

Organocatalytic Asymmetric Hetero-Diels-Alder Reaction of in Situ Generated Dienes: Access to α,ß-Unsaturated δ-Lactones Featuring CF3-Substituted Quaternary Stereocenter.

Chiral bifunctional urea-catalyzed asymmetric direct hetero-Diels-Alder reaction between alkylidene azlactone-derived dienes and trifluoromethyl aryl ketones is reported for the first time. The direct hetero-Diels-Alder reaction followed by ring opening results in densely functionalized α,ß-unsaturated δ-lactones featuring a CF3-substituted quaternary stereocenter in high yields with excellent enantioselectivities. The method is compatible over a range of substrates. Moreover, the reaction is scaled up and the α,ß-unsaturated δ-lactones were converted to amino acid derivatives decorated with trifluoromethylated carbinol functionality.

Enantioselective A3-Coupling Reaction Employing Chiral CuI- iPrpyboxdiPh/ N-Boc-(l)-Proline Complex under Cooperative Catalysis: Application in the Synthesis of (Indol-2-yl)methanamines.

An efficient route to enantioenriched propargylamines via a three-component alkynylation reaction using cooperative catalysis with a CuI- iPrpyboxdiPh complex and N-Boc-(l)-proline has been accomplished. A variety of functionalized amines, aldehydes, and 2-ethynyl anilines were reacted smoothly at ambient temperature to furnish a wide range of propargylamines in high yields (up to 94%) and excellent enantioselectivities (up to 98% ee). Synthetic utility of the methodology has been demonstrated by transforming the products into various synthetically useful intermediates. Finally, propargylamines were transformed into biologically important (indol-2-yl)methanamines over two steps in good yields (up to 88%) with an excellent level of enantioselectivities (up to 95%).