Practical Access to Fused Carbazoles via Oxidative Benzannulation and their Photophysical Properties.

An aryne annulation strategy for the synthesis of fused carbazoles is developed using indolyl ß-ketonitrile in a cascade manner. The reaction sequence involves aryne-mediated [2 + 2] cycloaddition cleavage and intramolecular Michael addition, followed by oxidation under transition-metal-free reaction conditions. Subsequently, conversion of benzo[b]carbazole-6-carbonitrile to carbazole quinone is observed upon prolongation of the reaction time. Furthermore, these materials exhibit high quantum efficiency, which promotes the light-emitting diode applications.

Stereo flexible synthesis of the C8-C23 fragment of antarlides, androgen receptor antagonists.

A practical and efficient synthesis of the C8-C23 fragment of antarlides A-H, incorporating six stereocenters and a conjugated diene, is reported. A strategic combination of synthetic methods, including CBS reduction, Evans' aldol reaction, Keck-Maruoka allylation, and enzymatic resolution, enabled the selective introduction of these stereocenters. Furthermore, the pivotal coupling of key fragments is successfully executed through a Julia-Kocienski olefination reaction, connecting the C8-C14 and C15-C23 subunits.

6-Strand to Stable 10/12 Helix Conformational Switch by Incorporating Flexible ß-hGly in the Homooligomers of Camphor Derived ß-Amino Acid: NMR and X-Ray Crystallographic Evidence.

Rational design of unnatural amino acid building blocks capable of stabilizing predictable secondary structures similar to protein fragments is pivotal for foldamer chemistry/catalysis. Here, we introduce novel ß-amino acid building blocks: [1S,2R,4R]exoCDA and [1S,2S,4R]endoCDA, derived from the abundantly available R(+)-camphor, which is traditionally known for its medicinal value. Further, we demonstrate that the homooligomers of exoCDA adopt 6-strand conformation, which switches to a robust 10/12-helix simply by inserting flexible ß-hGly spacer at alternate positions (1 : 1 ß-hGly/exoCDA heterooligomers), as evident by DFT-calculations, solution-state NMR spectroscopy and X-ray crystallography. To the best of our knowledge, this is the first example of crystalline-state structure of left-handed 10/12-mixed helix, that is free from the conventional approach of employing ß-amino acids of either alternate chirality or alternate ß2/ß3 substitutions, to access the 10/12-helix. The results also show that the homooligomers of heterochiral exoCDA don't adopt helical fold, instead exhibit banana-shaped strands, whereas the homodimers of the other diastereomer endoCDA, nucleate 8-membered turns. Furthermore, the homo-exoCDA and hetero-[ß-hGly-exoCDA] oligomers are found to exhibit self-association properties with distinct morphological features. Overall, the results offer new possibilties of constructing discrete stable secondary and tertiary structures based on CDAs, which can accommodate flexible residues with desired side-chain substitutions.

Construction of Octahydro-4H-cyclopenta[b]pyridin-6-one Skeletons using Pot, Atom, and Step Economy (PASE) Synthesis.

Cascade aza-Piancatelli reaction and [3+3]/[4+2] cycloaddition reactions are carried out using the ideality principles of pot, atom, and step economy (PASE) synthesis. The reaction resulted in generation of octahydro-4H-cyclopenta[b]pyridin-6-one scaffolds. Moreover, octahydro-5,7a-epoxycyclopenta[cd]isoindol-4-one frameworks of gracilamine alkaloid and a novel decahydro-1H-dicyclopenta[cd,hi]isoindol-6-one were also realized in good yields with excellent regio- and diastereo-selectivities.

Total synthesis of remdesivir.

Remdesivir, the first drug approved by the FDA to treat COVID-19, is in high demand for patients infected with the SARS-CoV-2 virus. Herein, we report a facile approach minimizing the protecting group manipulations to afford remdesivir in good overall yield.

Diastereoselective Formal Synthesis of Polycyclic Meroterpenoid (±)-Cochlearol A.

A formal synthesis of (±)-cochlearol A was accomplished. The synthesis features Suzuki coupling and Friedel-Crafts cyclization as a convergent strategy to the functionalized tetralone ring and an intramolecular construction of the C/D ring involving sequential epoxide formation/acetal formation.

More Twins in the Scientific Literature of the 21st Century.

This Essay highlights the complex issue of twinning in science publications. Historical accounts present cases where two scientists focused on the same problem and came up with the same solution following different paths. This has changed in the present day. The concurrent publication of rather similar research papers from different groups has increased in frequency since 2010. In the past, twinning in research publications was serendipitous, and there was a healthy competition among teams working on similar projects. Today, twinning has become more frequent. This can be attributed to the urge of researchers to have publications on popular topics, the tendency to base research programs on popular keywords, and funding agencies preferentially supporting certain areas of research. With vast amounts of literature being generated, editorial offices and referees may not be able to find these twins very easily. As we inch away from human ingenuity towards artificial intelligence, twinning may become even more frequent.

Metal Free Domino ß-Azidation/[3 + 2] Cycloaddition Reaction for the Synthesis of 1,2,3-Triazole-Fused Dihydrobenzoxazinones.

A metal free DBU catalyzed synthesis of 1,2,3-triazole-fused dihydrobenzoxazinone derivatives by tandem ß-azidation/[3 + 2] cycloaddition reaction has been developed under mild conditions. The methodological studies offer a broad scope and proceed well with a wide range of alkynylated cyclohexa 2,5-dienones, giving new cis-triazole-fused tricyclic scaffolds.

Total synthesis of (±)-galanthamine from GABA through regioselective aryne insertion.

The total synthesis of (±)-galanthamine is achieved in ∼5% overall yield using a key regioselective aryne insertion reaction into a GABA (γ-amino butyric acid) derivative. The strategy presented involves only two sub-critical temperature reactions and less than five chromatographic purifications to achieve the synthesis of galanthamine.

Strategies towards the synthesis of anti-tuberculosis drugs.

Antituberculosis drugs have captured the attention of the scientific community due to the emergence of drug resistance. Hence, the development of new analogs and new drugs which can treat drug-resistant tuberculosis is required. In this report, we reviewed the strategies towards the synthesis of antituberculosis drugs. These strategies include semisynthetic approaches, resolution based strategies, microbial transformations, solid phase synthesis, and asymmetric synthesis. As stereochemistry is an important hallmark of many drugs, the strategies based on asymmetric synthesis are described in detail. The emphasis on semisynthetic approaches is given for aminoglycoside antibiotics.

Editorial: The National Organic Symposium Trust-Shaping Organic Chemistry in India for Over 30 Years.

Reasons to celebrate! The National Organic Symposium Trust (NOST) celebrated its 30th anniversary in 2018. This organization has been instrumental in shaping and influencing organic chemistry research in India.

Syntheses of 2-Aroyl Benzofurans through Cascade Annulation on Arynes.

The highly efficient and expedient route for the syntheses of 2-aroyl benzofurans has been developed via the cascade [2+2] followed by a [4+1] annulation on arynes. The overall transformation proceeded through the formation of ortho-quinone methide by the insertion of transient aryne into N, N-dimethylformamide and subsequent trapping with sulfur ylide. Moreover, this transformation has a broad range of substrate scope with a high functional-group tolerance. This new reaction was successfully utilized in the synthesis of the potent CYP19 aromatase inhibitor and late-stage functionalization on the bioactive complex estrone.

Synthetic Strategy toward the Pentacyclic Core of Melodinus Alkaloids.

The three-component Povarov reaction is efficiently utilized for construction of the pentacyclic framework of complex Melodinus alkaloids, which is amenable to expansion to other complex natural products. The key steps were Povarov reaction, one-pot reductive cyclization, and ring-closing metathesis (RCM) reaction.

Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H.

Total syntheses of three different lamellarins have been accomplished using a Ru(II)-catalyzed (3 + 2) annulation strategy to construct the central pyrrole ring. The striking features of this synthesis are the use of PEG-400 as a green solvent for the (3 + 2) annulation reaction and multiple catalytic reactions with excellent overall yield. The present route also enables the synthesis of various lamellarin analogues devoid of a B ring.

Expanding the tetrahydroquinoline pharmacophore.

Tetrahydroquinoline is a privileged scaffold with a large number of biological applications. The tetrahydroquinoline pharmacophore has been expanded to yield 34 compounds. Biological screening of these compounds led to the identification of tetrahydroquinoline as neurotropic agents not reported earlier.

Insertion of N-Tosylacetimidates/Acetimidamides onto Arynes via [2 + 2] Cycloaddition.

A novel insertion reaction of N-tosylacetimidates and N-tosylacetimidamides onto arynes via a benzocyclobutene intermediate followed by ring cleavage is developed to afford o-benzylbenzoic acid derivatives in good yields. Interestingly, the use of cyclic 2-sulfonyliminoindolines provided two distinct products such as azepanimines via [2 + 2] cycloaddition and indolamines via protonation based on solvent medium.

The Ireland-Claisen rearrangement strategy towards the synthesis of the schizophrenia drug, (+)-asenapine.

(±)-Asenapine, sold in the market as Saphris/Sycrest for the treatment of bipolar disorders, is synthesized in an optically pure form involving an Ireland-Claisen rearrangement as the key step. This approach allows access to all diastereomers.

α-Hydroxyallylsilanes as propionaldehyde enolate equivalents and their use toward iterative aldol reactions.

Smooth and efficient reaction conditions have been found for the transformation of protected ß-hydroxyacylsilanes into the corresponding aldehydes. This opens a new route to iterative aldol reactions, and it has been used for the synthesis of fragments of several bioactive natural products.

Scalable synthesis of the unusual amino acid segment (ADMOA unit) of marine anti-inflammatory peptide: solomonamide A.

The most abundantly available hexose sugar, d-glucose has been converted to protected 4-amino(2'amino-4'-hydroxy phenyl)-3,5-dihydroxy-2-methyl-6-oxo hexanoic acid (protected ADMOA, 3), the unusual amino acid present in marine natural product solomonamide A in gram quantities involving easy to operate chemical transformations.

Total synthesis of a thromboxane receptor antagonist, terutroban.

A total synthesis of terutroban is achieved using the Claisen rearrangement, Friedel-Crafts acylation and Heck coupling as key reactions, avoiding the classical Diels-Alder approach used before.