Transforming an azaarene into the spine of fusedbicyclics via cycloaddition-induced scaffold hopping of 5-Hydroxypyrazoles.

Skeleton editing for heteroarenes, especially pyrazoles, is challenging and remains scarce because these non-strained aromatics exhibit inert reactivities, making them relatively inactive for performing a dearomatization/cleavage sequence. Here, we disclose a cycloaddition-induced scaffold hopping of 5-hydroxypyrazoles to access the pyrazolopyridopyridazin-6-one skeleton through a single-operation protocol. By converting a five-membered aza-arene into a five-unit spine of a 6/6 fused-bicyclic, this work unlocks a ring-opening reactivity of the pyrazole core that involves a formal C = N bond cleavage while retaining the highly reactive N-N bond in the resulting product.

Iodine as Polarity-Reversal Catalyst: Synthesis of a Fused Heterocycle with Contiguous Stereocenters.

We report an unconventional I-catalyzed cascade reaction for the synthesis of angular triquinane derivatives with a fused heterocycle skeleton, leveraging enaminones and anilines as simple acyclic precursors. The key to success lies in I functioning as a polar-reversal catalyst, which alters the reactivity at the α-position of the enaminone and facilitates the first hexa-functionalization of an enaminone along with the formation of highly congested continuous stereocenters.

Synthesis of 6--Spiro[4.5]decane Derivatives by Merging Ring-Opening of Benzo[]oxepines and Formal 1,2-Oxygen Migration.

A facile one-pot synthetic method has been developed for constructing 6--spiro[4.5]decane skeletons by merging the ring-opening of benzo[]oxepines and formal 1,2-oxygen migration reactions. More than 30 examples of the 6--spiro[4.

I-Induced Umpolung: Synthesis of a 1,6-Dihydrofuro[3,2-]pyrazolo[3,4-][1,4]thiazine Skeleton via an Unconventional 1,4-Dithiane-2,5-diol Reaction Mode.

In this paper, novel sulfur-containing 1,6-dihydrofuro[3,2-]pyrazolo[3,4-][1,4]thiazine skeletons were constructed from the simple and readily available materials enaminone, 5-aminopyrazole, and 1,4-dithiane-2,5-diol. Furthermore, a novel 1,4-dithiane-2,5-diol reaction mode has been developed through a double-dipole-reversal process induced by iodine that results in the formation of six new bonds and two new rings in a one-pot reaction. This method shows good substrate compatibility, and the products can be further modified with a variety of pharmaceuticals.

Divergent synthesis of pyrrolidone fused pyrimido[1,2-]indazole through selective trapping of an enone intermediate by 1-indazol-3-amine.

An oxidant-controlled divergent synthesis of a pyrrolidone fused pyrimido[1,2-]indazole skeleton was developed through selective cyclization of an generated enone intermediate and 1-indazol-3-amine. The one-pot, metal-free process formed three C-N bonds, one C-C bond, and a tetrasubstituted carbon stereocenter containing a hydroxyl group. This method not only allowed for the synthesis of over 60 new pyrrolidone fused pyrimido[1,2-]indazole derivatives, but was also compatible with the transformation of complex active molecules and the derivation of target products.

One Stone, Three Birds: One-Pot Synthesis of Pyrido[3,2-]phenoxazin-5-one Derivatives from -Aminophenols with Triple Roles, Paraformaldehyde, and Enaminones via the Povarov Reaction.

A novel multicomponent cascade cyclization reaction in one pot for the preparation of pyrido[3,2-]phenoxazin-5-ones from simple -aminophenols, paraformaldehyde, and enaminones has been established. It is noteworthy that -aminophenol plays multiple roles serving as both a bis-nucleophile and an iminoquinone precursor, which can in situ generate aminophenoxazinones to undergo the Povarov reaction for the first time to yield pyrido[3,2-]phenoxazin-5-ones with a high efficiency. Moreover, the photoluminescence of pyrido[3,2-]phenoxazin-5-ones has polarity sensitivity and features aggregation-induced emission (AIE) characteristics, which is promising for bioimaging and theranostic applications.

I-Promoted -Diarylethene Involved Aza-Diels-Alder Reaction and Wagner-Meerwein Rearrangement: Construction of 2,3,4-Trisubstituted Pyrimido[1,2-]indazole Skeletons.

A [3 + 1 + 2] cyclization-rearrangement reaction scheme was developed to synthesize pyrimido[1,2-]indazoles from aryl methyl ketones, 3-aminoindazoles, and -diarylethenes. This metal-free process proceeds via a sequential aza-Diels-Alder reaction and Wagner-Meerwein rearrangement, and a possible reaction mechanism was demonstrated based on control experiments. This method exhibits good substrate compatibility and allows simple reaction conditions.

Direct Hydrodefluorination of CF-Alkenes via a Mild S2' Process Using Rongalite as a Masked Proton Reagent.

A concise and efficient hydrodefluorination process was developed for the synthesis of -difluoroalkenes. This reaction employs rongalite as a masked proton source and does not require any additional catalysts or reductants. Notably, trifluoromethyl alkenes having both terminal and internal double bonds are compatible with this process, allowing for a wider range of substrates.

A Pummerer Reaction-Enabled Modular Synthesis of Alkyl Quinoline-3-carboxylates and 3-Arylquinolines from Amino Acids.

Concise synthesis of functionalized quinolines has received continuous research attention owing to the biological importance and synthetic potential of bicyclic -heterocycles. However, synthetic routes to the 2,4-unsubstituted alkyl quinoline-3-carboxylate scaffold, which is an important motif in drug design, remain surprisingly limited, with modular protocols that proceed from readily available materials being even more so. We herein report an acidic I-DMSO system that converts readily available aspartates and anilines into alkyl quinoline-3-carboxylate.

Aniline assisted dimerization of phenylalanines: convenient synthesis of 2-aroyl-3-arylquinoline in an I-DMSO system.

We herein report an efficient synthesis of 2-aroyl-3-arylquinolines from phenylalanines and anilines. The mechanism involves I-mediated Strecker degradation enabled catabolism and reconstruction of amino acids and a cascade aniline-assisted annulation. Both DMSO and water act as oxygen sources in this convenient protocol.

I-Promoted In Situ Cyclization-Rethiolation Reaction: Synthesis of 2-Aliphatic- or Aromatic-Substituted Indolizines.

An efficient I-promoted one-pot one-step three-component reaction for the synthesis of sulfhydryl indolizines from methyl ketones, 2-pyridylacetate derivatives, and sulfonyl hydrazides via an in situ cyclization-rethiolation strategy has been developed. This protocol shows excellent substrate compatibility, including for chain and cyclic aliphatic methyl ketones, natural product pregnenolone acetate, and phosphorus-containing methyl ketones, affording a series of valuable aliphatic-substituted indolizines in good yields.

One-Pot Synthesis of Diaryl 1,2-Diketones via Zn-Mediated Reductive Coupling.

A reductive coupling reaction was established for the synthesis of diaryl 1,2-dicarbonyl compounds from aryl methyl ketones in good yields. The mechanistic study showed the reaction undergoes C(CO)-C(sp) bond cleavage, with the reductive coupling reaction occurring through an electron transfer process. Notably, the reaction not only is simple to operate but also has mild reaction conditions and a wide range of applicable substrates.

Synthesis of Tetrahydro-2-thiopyran 1,1-Dioxides via [1+1+1+1+1+1] Annulation: An Unconventional Usage of a Tethered C-S Synthon.

An unprecedented [1+1+1+1+1+1] annulation process has been developed for the construction of tetrahydro-2-thiopyran 1,1-dioxides. Notably, rongalite acted as a tethered C-S synthon in this reaction and can be chemoselectively used as triple C1 units and as a source of sulfone. Mechanistic investigation indicated that two different carbon-increasing models are involved in this reaction in which rongalite serves as C1 units.

Pd-Catalyzed Hydroxyl-Directed Cascade Hydroarylation/C-H Germylation of Nonterminal Alkenes and Aryl Iodides.

Pd-catalyzed cascade hydroarylation and C-H germylation of nonterminal alkenes and aryl iodides enabled by hydroxyl assistance have been developed. The key step in this C-H germylation cascade is the formation of a highly reactive oxo-palladacycle intermediate, which markedly restrained the β-H elimination process. Mechanistically, control experiments indicated that the hydroxyl group played an important role in this process.

Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives.

A robust, practical, and scalable approach for the construction of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives via the addition of Grignard reagents to 4-amino-2-chloronicotinonitrile () was developed. Starting with various Grignard reagents, a wide range of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives were conveniently synthesized in moderate-to-good yields through addition-acidolysis-cyclocondensation. In addition, the robustness and applicability of this synthetic route was proven on a 100 g scale, which would enable convenient sample preparation in the preclinical development of 1,6-naphthyridin-4-one-based MET-targeting antitumor drug candidates.

[Relationship between cytoplasmic phospholipase A2 and nuclear factor κB in one lung ventilation-induced lung injury in rabbits].

Objective: To elucidate the mechanisms of up regulated expression of cytoplasmic phospholipase A2 (CPLA2) induced by one lung ventilation (OLV) by investigating the interactions between nuclear factor kappaB (NF-κB) and C-PLA2.

Methods: Forty-eight healthy Japanese white rabbits were randomized into control group, solvent treatment group (group S), NF-κB inhibitor (PDTC)/solvent treatment group ( group PS), C-PLA2 inhibitor (AACOCF3)/solvent treatment group (group AS), OLV group (group O), solvent treatment plus OLV group (SO group), NFκB inhibitor (PDTC)/solvent treatment plus OLV group (group PSO) and CPLA2 inhibitor (AACOCF3)/solvent treatment plus OLV group (group ASO). ELISA was used to detect arachidonic acid (AA) content in the lung tissues, and NFκB and CPLA2 expressions were detected by Western blotting and quantitative PCR.