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The synthesis of pyrimidine‐spirofused indolines from 1,3,5‐triazinanes with 2‐sulfonyliminoindolines has been achieved under catalyst‐ and additive‐free conditions, in which five atoms of 1,3,5‐triazinanes were introduced to the spiro‐annulation products via a (5+1) pathway. Subsequently, this strategy was extended to 3‐aminoindoles and 3‐aminobenzothiophenes, but a different reaction pathway (3+3) was observed. In these cases, three‐atoms of 1,3,5‐triazinanes were incorporated into pyrimidine‐fused indoles/benzothiophenes. These two transformations demonstrate the potential and versatility of 1,3,5‐triazinanes to construct nitrogen‐heterocycles. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A metal‐free, green, and sustainable functionalization of unactivated alkyl sp3 C—H bonds is reported using iodine(III) as a feasible dehydrogenation agent under visible light or KBr, and alkyl chlorides, bromides, alcohols, and ketones could be constructed by addition of different coupling reagents. Cheap and safe iodobenzene diacetate was used to form a radical to activate the alkyl sp3 C—H bond in a highly efficient manner, which can construct different alkylation products by adding corresponding coupling reagents. [ABSTRACT FROM AUTHOR]

Carbenes are pivotal reactive intermediates for accessing a wide range of complex molecules, which are frequently used in chemical synthesis and medicinal advancement. We have developed a convenient approach to fluorenes from α‐biaryldiazoacetates via low‐energy blue light‐induced photochemical generation of a carbene intermediate, where the reaction took place at room temperature without any catalysts, bases, or oxidants in acetonitrile. The present catalyst‐free and operationally simple approach enables highly efficient annulation of α‐biaryldiazoacetates under mild reaction conditions. [ABSTRACT FROM AUTHOR]

The main protease (Mpro) of SARS‐CoV‐2 is a well‐characterized target for antiviral drug discovery. To date, most antiviral drug discovery efforts have focused on the S4–S1′ pocket of Mpro; however, it is still unclear whether the S1′–S3′ pocket per se can serve as a new site for drug discovery. In this study, the S1′–S3′ pocket of Mpro was found to differentially recognize viral peptidyl substrates. For instance, S3′ in Mpro strongly favors Phe or Trp, and S1′ favors Ala. The peptidyl inhibitor D‐4–77, which possesses an α‐bromoacetamide warhead, was discovered to be a promising inhibitor of Mpro, with an IC50 of 0.95 μM and an antiviral EC50 of 0.49 μM. The Mpro/inhibitor co‐crystal structure confirmed the binding mode of the inhibitor to the S1′–S3′ pocket and revealed a covalent mechanism. In addition, D‐4–77 functions as an immune protectant and suppresses SARS‐CoV‐2 Mpro‐induced antagonism of the host NF‐κB innate immune response. These findings indicate that the S1′–S3′ pocket of SARS‐CoV‐2 Mpro is druggable, and that inhibiting SARS‐CoV‐2 Mpro can simultaneously protect human innate immunity and inhibit virion assembly. [ABSTRACT FROM AUTHOR]

The daphnezomine A‐type subfamily of Daphniphyllum alkaloids structurally features a unique aza‐adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (−)‐daphnezomines A and B and (+)‐dapholdhamine B have been accomplished in 16–20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti‐mediated radical cyclization to establish the azabicyclo[3.3.1]nonane ring system, an intramolecular Heck reaction to install the bridgehead all‐carbon quaternary stereocenter, a tandem deprotection/reduction/keto amine‐carbinolamine tautomerization to furnish the aza‐adamantane backbone, and an NIS‐promoted 6‐endo‐trig aminocyclization to assemble the (+)‐dapholdhamine B backbone. [ABSTRACT FROM AUTHOR]

An array of spiro[benzofuran-2,3′-pyrazol]-3-imines with diverse functional groups were readily assembled from aurone-derived azadienes and in - situ generated nitrilimines under mild conditions. The transformation was performed in a regio- and diastereoselective fashion, in which a synergetic [2+3] cycloaddition pathway was likely involved. This novel methodology has extended the synthetic application of aurone-derived azadienes as a kind of two-atom synthon. [ABSTRACT FROM AUTHOR]

The synthesis of 4‐(trifluoromethyl)‐2,3‐dihydrothiazoles from α‐enolic dithioesters and imidoyl sulfoxonium ylides has been achieved under thermal conditions. This transformation is catalyst‐free, additive‐free, and operationally simple, and it proceeds via a formal insertion of alkenyl S−H generated in situ from dithioesters into ylides followed by an intramolecular annulation. This approach further expands the synthetic application of two versatile sulfur‐containing building blocks of fluorinated imidoyl sulfoxonium ylides and α‐enolic dithioesters. [ABSTRACT FROM AUTHOR]

Switchable approaches to accomplish the C3-aminomethylation and C3-arylmethylation of imidazo[1,2-a]pyridines with N-methylanilines using distinct electrochemical conditions have been developed. These two transformations exhibited notable regio- and chemoselectivities under air and metal/oxidant-free conditions. Remarkably, the environmentally benign electrochemical methods could be extended to the late-stage derivatization of natural products and drugs using N-methyl amines as a 1C source. [ABSTRACT FROM AUTHOR]

Phospholipids (PLs) are important components of physiological metabolism in animals and plants, and they have been widely used in clinical treatment, cosmetics, and industry. With the development of marine resources, marine PLs rich in polyunsaturated fatty acids have attracted increasing attention. As important marine resources, shrimp heads (SH), codfish roe (CR), and squid gonads (SG) contain a high PL content. The antithrombotic, antistroke, anti‐inflammatory, pro‐angiogenic, and cardioprotective activities of PLs from SH, CR, and SG were evaluated and compared using the in vivo zebrafish model. The results showed that the PL extracts of SH, CR, and SG had significant biological activities, which lays a theoretical foundation for the development and utilization of PLs in marine byproducts in the future, providing a new choice for the prevention of inflammatory and cardiovascular diseases. Practical applications: In this experiment, phospholipids in seafood from different sources were extracted, and their biological activities were comprehensively evaluated and compared using the zebrafish model to lay a foundation for the development of cardiovascular drugs, health food, special medicinal food, and other effective components. The utilization of marine byproducts not only makes full use of resources, but it also protects the environment. [ABSTRACT FROM AUTHOR]

An electrochemical decarboxylative aminomethylation reaction of imidazo[1,2‐a]pyridines with various N‐substituted glycines in acetonitrile at room temperature has been described. The reaction could be conducted under light‐free, catalyst‐free, oxidant‐free, and air conditions, affording the C3‐aminomethylated imidazo[1,2‐a]pyridines in good to high yields. Remarkably, N‐aryl, N,N‐dialkyl, and N‐alkyl‐N‐aryl glycines are all well‐tolerated in this easily handled protocol, which further expands the chemical space of bioactive imidazo[1,2‐a]pyridine derivatives. [ABSTRACT FROM AUTHOR]

Research has been conducted on the preparation of the conformationally restricted nicotinoid from D- and L-glutamic acid. The pyroglutamic acid derivative coupling with ortho-lithiated 4-chloropyridine is described.

A formal (3+2) annulation reaction between isatin-derived N -tosylhydrazones and o -(trimethylsilyl)aryl triflates allows facile synthesis of spiro[indazole-3,3′-indolin]-2′-ones in high to excellent yields. Furthermore, indazolo[2,3- c ]quinazolin-6(5 H)-ones could be accessed from the same starting materials in one-pot fashion via an annulation/rearrangement pathway. [ABSTRACT FROM AUTHOR]

(+)‐Mannolide C is a complex hexacyclic C20 cephalotane‐type diterpenoid featuring a highly strained 7/6/6/5 tetracyclic core containing eight consecutive stereocenters and two bridging lactones. The first asymmetric total synthesis of (+)‐mannolide C has been accomplished by lipase‐mediated resolution, Ru‐complex‐catalyzed double ring‐closing metathesis (RCM) reactions, NiII‐catalyzed diastereoselective Michael addition, and MnIII‐catalyzed allylic oxidation as the key transformations. [ABSTRACT FROM AUTHOR]

A facile access to thiazolidin-4-ones from α-enolic dithioesters and α-halohydroxamates in situ derived active 1,3-dipolar aza-oxyallyl cations was achieved under mild conditions. These five-membered heterocycles with Z-exocyclic double bonds and diverse substituents can be readily obtained via a regio- and stereoselective formal [3+2] cycloaddition pathway. [ABSTRACT FROM AUTHOR]

An efficient annulation reaction of aurone-derived α,β-unsaturated imines and activated terminal alkynes mediated by triethylamine is described, which enables the facile synthesis of 1,4-dihydrobenzofuro[3,2-b]pyridines in high yields. When the nucleophile of triethylamine was replaced with triphenylphosphine, another class of 1,4-dihydrobenzofuro[3,2-b]pyridines tethered with an additional acrylate motif were obtained instead. These two types of 1,4-dihydrobenzofuro[3,2-b]pyridines could be aromatized in the presence of DBU to afford benzofuro[3,2-b]pyridines, which could also be accessed via a one-pot procedure. [ABSTRACT FROM AUTHOR]

An efficient, one-pot, three-component [3+2] cycloaddition reaction of azomethine ylide obtained from α-dicarbonyl compounds (cyclic and acyclic diketone or keto ester) and amino acids with maleimides under catalyst-free conditions has been developed. This cascade protocol shows high efficiency and remarkable functional group tolerance, and the ubiquitous succinimide-fused pyrrolizidines with a highly compact and strained scaffold were obtained with high yield and excellent diastereoselectivity. Furthermore, this novel and atom-economical strategy could be performed on a gram scale with comparable reaction efficiency. [ABSTRACT FROM AUTHOR]

The synthesis of hydrobenzoimidazoles from para‐quinamines and 1,3,5‐triazinanes was achieved via a formal [3+2] annulation reaction in the presence of In(OTf)3 as the catalyst. Further studies demonstrated that the synthesis of hydrobenzooxazoles could also be accomplished via the same strategy from para‐quinols and 1,3,5‐triazinanes. [ABSTRACT FROM AUTHOR]

The synthesis of pyridothiazepines has been achieved via a 1,5‐dipolar cycloaddition reaction between pyridinium 1,4‐zwitterionic thiolates and activated allenes conducted under thermal conditions. Meanwhile, a ring‐contraction reaction of the resulting pyridothiazepine derivatives via the extrusion of 3‐thioxoacrylates has also been described. [ABSTRACT FROM AUTHOR]

A [4+2] annulation reaction of 1,3,5‐triazinanes and aurone‐derived α,β‐unsaturated imines has been developed, which enables the synthesis of 1,2,3,4‐tetrahydrobenzofuro[3,2‐d]pyrimidines under thermal conditions in high yields. This protocol is catalyst‐free and additive‐free. [ABSTRACT FROM AUTHOR]

Cyclopianes are novel diterpenes featuring a highly strained 6/5/5/5 tetracyclic core embedded with 6–8 consecutive stereocenters. The concise total syntheses of (−)‐conidiogenone B, (−)‐conidiogenone, and (−)‐conidiogenol have been accomplished in 14–17 steps. The present work features a HAT‐mediated alkene–nitrile cyclization to access the cis‐biquinane, a Nicholas/Pauson–Khand reaction to construct the linear triquinane, and a Danheiser annulation to afford the congested angular triquinane skeleton. [ABSTRACT FROM AUTHOR]