Diastereoselective construction of bridged piperidines through an interrupted dearomative reduction.

An interrupted dearomative reduction strategy was developed to transform planar chalcone-based pyridinium salts into structurally intriguing bridged piperidines in a completely regio- and diastereoselective manner. This reaction proceeded successfully by using cheap and easily accessible NaBH4 as the reductant under mild conditions without exclusion of oxygen or use of special equipment.

A combination of polarity reversal, Diels-Alder cycloaddition and skeletal remodeling to access pyridine-fused nitrones.

An unprecedented cascade strategy consisting of polarity reversal, normal electron-demand Diels-Alder cycloaddition and skeletal remodeling was developed to construct novel pyridine-fused nitrones in up to 82% yield. The key to the success was the umpolung process, which transformed the electron-deficient 3-nitropyridinium ring into a reactive, π-extended cyclic nitroalkene, serving as a rarely reported hetero-diene to participate in normal Diels-Alder cycloadditions.

Dearomative Periphery Modification of Quinolinium Salts to Assemble Ring-Encumbered Pyrrolidine-Tetrahydroquinoline Polycycles.

We report an unexpected dearomative periphery modification strategy for transforming quinolinium salts into structurally crowded pyrrolidine-tetrahydroquinoline polycyclic systems with complete regio- and diastereoselectivity. Importantly, the reaction pathway was regulated by simply tuning the substituents, achieving substituent-directed divergent synthesis. The notable features of this transformation include readily available starting materials, green conditions, a simple workup procedure, high bond- and ring-forming efficiency, and substituent-directed diverse synthesis.

Construction of bridged polycycles through dearomatization strategies.

Bridged polycycles are privileged molecular skeletons with wide occurrence in bioactive natural products and pharmaceuticals. Therefore, they have been the pursing target molecules of numerous chemists. The rapid and convenient generation of sp3-rich complex three-dimensional molecular skeletons from simple and easily available aromatics has made dearomatization a highly valuable synthetic tool for the construction of rigid and challenging bridged rings. This review summarizes the-state-of-the-art advances of dearomatization strategies in the application of bridged ring formation, discusses their advantages and limitations and the in-depth mechanism, and highlights their synthetic value in the total synthesis of natural products. We wish this review will provide an important reference for medicinal and synthetic chemists and will inspire further development in this intriguing research area.

Assembly of functionalized π-extended indolizine polycycles through dearomative [3+2] cycloaddition/oxidative decarbonylation.

Reported herein is an unexpected construction of functionalized π-extended indolizine polycycles through a one-pot two-step cascade process comprising the base-promoted dearomative [3+2] cycloaddition of quinilinium salts and 3-alkenyl oxindoles, followed by a DDQ-mediated oxidative decarbonylation. Moreover, we could achieve the substrate-controlled diverse synthesis of structurally strained cyclopropane spirooxindole by using pyridinium salts as starting materials.

Skeletal remodeling of chalcone-based pyridinium salts to access isoindoline polycycles and their bridged derivatives.

Simultaneous deconstructive ring-opening and skeletal reconstruction of an inert, aromatic pyridinium ring is of great importance in synthetic communities. However, research in this area is still in its infancy. Here, a skeletal re-modeling strategy was developed to transform chalcone-based pyridinium salts into structurally intriguing polycyclic isoindolines through a dearomative ring-opening/ring-closing sequence. Two distinct driving forces for the deconstruction of the pyridinium core were involved in these transformations. One was the unprecedented harnessing of the instability of in situ generated cyclic ß-aminoketones, and the other was the instability of the resultant N,N-ketals. The desired isoindoline polycycles could undergo the Wittig reaction with various phosphorus ylides to achieve structural diversity and complexity. Notably, by tuning the Wittig conditions by addition of one equivalent of base, an additional bridged ring was introduced. A plausible mechanism was proposed on the basis of control experiments and theoretical calculations.

Chalcone-Based Pyridinium Salts and Their Diastereoselective Dearomatization To Access Bibridged Benzoazepines.

New chalcone-based pyridinium salts have been successfully exploited, which could smoothly participate in the highly diastereoselective dearomatization with binucleophilic enaminones by taking advantage of their multiple reactive sites to construct bibridged benzoazepines in up to 89% yields. The key to the success was the skillful and unprecedented C-3 functionalization of the new pyridinium salts. This work not only provides a kind of novel pyridinium salt synthon but also achieves the first C-3 functionalization of pyridinium salts to construct complex and challenging bibridged benzoazepines with high synthetic efficiency.

An unexpected cascade reaction of 3-hydroxyoxindoles with coumarin-3-carboxylates to construct 2,3-dihydrobenzofuran spirooxindoles.

An unexpected Michael addition-inspired ring-opening/closure cascade reaction of 3-hydroxyoxindoles with coumarin-3-carboxylates was developed to access new dihydrobenzofuran or dihydrobenzothiophene spirooxindoles in 68-98% yields. This reaction not only provides an expedient and convenient method to assemble dihydrobenzofuran spirooxindoles, but also establishes a new reaction mode of coumarin-3-carboxylates. Moreover, it represents the first example of 3-hydroxyoxindoles serving as a C1 synthon possessing dual nucleophilic and electrophilic character with the hydroxyl group as a leaving group. Importantly, this methodology provides a rapid and robust approach to XEN907 analogues.

Regio- and diastereoselective dearomatizations of N-alkyl activated azaarenes: the maximization of the reactive sites.

An unprecedented base-promoted multi-component one-pot dearomatization of N-alkyl activated azaarenes was developed, which enabled the synthesis of complex and diverse bridged cyclic polycycles with multiple stereocenters in a highly regio- and diastereoselective manner. Besides, we realized the step-controlled dearomative bi- and trifunctionalization of quinolinium salts. These transformations not only achieved the maximization of the reaction sites of pyridinium, quinolinium and isoquinolinium salts to enhance structural complexity and diversity, but also opened up a new reaction mode of these N-activated azaarenes. A unique feature of this strategy is the use of easily accessible and bench-stable N-alkyl activated azaarenes to provide maximum reactive sites for dearomative cascade cyclizations. In addition, the salient characteristics including high synthetic efficiency, short reaction time, mild conditions and simple operation made this strategy particularly attractive.

Microarray analysis of adipose tissue gene expression profiles between two chicken breeds.

The chicken is an important model organism that bridges the evolutionary gap between mammals and other vertebrates and provides a major protein source from meat and eggs throughout the world. Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by the broiler industry nowadays. In order to visualize the mechanisms involved in the gene expression and regulation of lipid metabolism in adipose tissue, cDNA microarray containing 9024 cDNA was used to construct gene expression profile and screen differentially expressed genes in adipose tissue between broilers and layers of 10 wk of age. Sixty-seven differentially expressed sequences were screened out, and 42 genes were found when blasted with the GenBank database. These genes are mainly related to lipid metabolism, energy metabolism, transcription and splicing factor, protein synthesis and degradation. The remained 25 sequences had no annotation available in the GenBank database. Furthermore, Northern blot and semi-quantitative RT-PCR were developed to confirm 4 differentially expressed genes screened by cDNA microarray, and it showed great consistency between the microarray data and Northern blot results or semi-quantitative RT-PCR results. The present study will be helpful for clarifying the molecular mechanism of obesity in chickens.