Diversity-oriented synthesis of indole-fused scaffolds and bis(indolyl)methane from tosyl-protected tryptamine.

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-ß-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-ß-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

Dearomatization of 3-Aminophenols for Synthesis of Spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones via Hydride Transfer Strategy-Enabled [5+1] Annulations.

The Sc(OTf)3-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones. The "two-birds-with-one-stone" strategy was disclosed by the dearomatization of phenols and direct α-C(sp3)-H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure.

Controllable Synthesis of N-Heterocycles via Hydride Transfer Strategy-Enabled Formal [5 + 1] and [5 + 2] Cyclizations.

The Brønsted acid-controlled switchable synthesis of indoline-fused tetrahydroquinolines and indole-fused benzazepines was developed through hydride transfer-enabled formal [5 + 1] and [5 + 2] cyclization reactions from indoles and N-alkyl o-aminobenzoketones. Indoline, furanone, and tetrahydroquinoline hybridized pentacyclic products were unprecedentedly accessed via a cascade condensation/hydride transfer/dearomatization-cyclization/deethylation/nucleophilic addition process. In addition, the undeveloped hydride transfer-involved [5 + 2] cyclizations were also realized for direct construction of indole-fused benzazepines.

Controllable Synthesis of N- and O-Containing Heterocycles via Formal [3 + 2] and [5 + 2] Cyclizations.

The controllable synthesis of spirooxindole-dihydrofurans and spirooxindole-benzazepines was developed through formal [3 + 2] and [5 + 2] cyclization reactions from 2-(2-oxoindolin-3-yl)malononitriles and ortho-aminobenzaldehydes, respectively. A variety of spirooxindole-benzazepines were facilely constructed via a furan ring-open-involved hydride transfer/cyclization process. It is noteworthy that the application of the hydride-transfer-involved [5 + 2] cyclization strategy for construction of spirobenzazepines was unprecedented. In addition, the spiro N- and O-containing heterocycles were highly functionalized by amino, amide, and cyano groups, which were conducive to late-stage functionalization.

Alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions.

The use of alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions represents a promising strategy that greatly enriches redox-neutral hydride transfer chemistry. This review summarizes the remarkable progress made in this field, and focuses on (1) alkyl amines as traceless hydride donors in cascade [1,5]-hydride transfer/elimination reactions and (2) alkyl ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions. The reaction mechanisms, features, scope, limitations, and synthetic applications are included, where appropriate. Importantly, its powerful ability in allene synthesis and the combination with [Re]-vinylidene and carbocation chemistries render this strategy attractive enough to inspire chemists to develop colorful reactions for building molecular complexity.

Redox-Triggered Switchable Synthesis of 3,4-Dihydroquinolin-2(1H)-one Derivatives via Hydride Transfer/N-Dealkylation/N-Acylation.

The switchable synthesis of 3-non, 3-mono, 3,3'-disubstituted 3,4-dihydroquinolin-2(1H)-ones was developed through a redox-neutral hydride-transfer/N-dealkylation/N-acylation strategy from o-aminobenzaldehyde with 4-hydroxycoumarin, and Meldrum's acid, respectively. The unprecedented strategy for the synthesis of 3,3'-highly functionalized 3,4-dihydroquinolin-2(1H)-one has been realized with the in situ utilization of the released HCHO via the o-QM involved Michael addition. In addition, the synthetic utility of this protocol has been well illustrated via concise synthesis of CYP11B2 inhibitor.

Hydrogen-bonding-assisted redox-neutral construction of tetrahydroquinolines via hydride transfer.

The hydrogen-bonding-assisted construction of tetrahydroquinolines decorated with structurally diverse 3,3'-difunctional groups has been realized via a hydride transfer-involved three-step cascade reaction in the presence of morpholine. This protocol solves the limitation of acyclic 1,3-dicarbonyl compounds by one-pot synthesis of tetrahydroquinolines, featuring operational simplicity, broadly applicable substrates, and metal- and acid-free conditions with EtOH as a hydrogen-bonding donor.

The protective effects of long non-coding RNA-ANCR on arterial calcification.

INTRODUCTION: Arterial calcification is a major factor for cardiovascular events and is characterized by vascular smooth muscle cells (VSMCs) transformed into osteoblast-like cells. Long non-coding RNAs (lncRNA) were recognized as important regulators of diverse biological processes. Previous studies have demonstrated that lncRNAs could regulate the proliferation and apoptosis of VSMCs. LncRNA-ANCR (Anti-differentiation ncRNA) is an essential mediator governing the differentiation of human osteoblast. However, it is unclear whether ANCR could regulate the osteoblastic differentiation of VSMCs. In this study, we determined the effect of ANCR on VSMCs differentiation and arterial calcification. MATERIALS AND METHODS: Both cellular and mouse model of arterial calcification were, respectively, established to investigate the role of ANCR in the mechanism of arterial calcification. ANCR overexpressing lentivirus were used to investigate the effects of ANCR on the expression of bone proteins and autophagy-related molecules. RESULTS: ANCR could inhibit ß-glycerophosphate (ß-GP)-induced VSMCs osteoblastic differentiation and mineralization due to decreased expressions of Runt-related transcription factor 2, bone morphogenetic protein-2, and formation of mineralized nodule, and attenuate high calcitriol-induced mice model of arterial calcification. Furthermore, ANCR could significantly increase LC3 and autophagy protein 5 expression in ß-GP-stimulated VSMCs, and the effect could be inhibited by 3-methyladenine, a pharmacological inhibitor of autophagy. CONCLUSION: ANCR may inhibit the osteoblastic differentiation of VSMCs and attenuate mice arterial calcification through activating autophagy.

Aromatization-Driven Cascade [1,5]-Hydride Transfer/Spirocyclization Promoted by Fluorinated Alcohols.

The aromatization-driven redox-neutral cascade [1,5]-hydride transfer/spirocyclization and cascade [1,5]-hydride transfer/hydrolysis from para-quinone methide in HFIP were developed. These protocols enabled the synthesis of azaspirocyclohexadienones and ortho-benzylated anilines in good to high yields under mild conditions, featuring room temperature, additive-free, and good functional group tolerance.

IrIII -Catalyzed One-Pot Cascade Synthesis of Pentacyclic-Fused Carbazoles from Indoles and Diazoes.

A highly efficient IrIII -catalyzed cascade cyclization of indoles and diazoes giving access to unique pentacyclic-fused carbazoles has been developed. This novel strategy expanded the application scope of coupling partners to take diazo compounds as a C2 source, and two new cycles, three new C-C and one new C-N bonds were formed in one-pot.

Highly enantioselective [3+2] coupling of cyclic enamides with quinone monoimines promoted by a chiral phosphoric acid.

Enantioselective [3+2] coupling of cyclic enamides with quinone monoimines was realised using a chiral phosphoric acid as a catalyst. This transformation allowed for the synthesis of highly enantioenriched polycyclic 2,3-dihydrobenzofurans (up to 99.9% ee). The absolute configuration of one product was determined by an X-ray crystal structural analysis. We also found a possible mechanism for this reaction.

Enantioselective Recognition of Chiral Carboxylic Acids by a ß-Amino Acid and 1,10-Phenanthroline Based Chiral Fluorescent Sensor.

A novel chiral 1,10-phenanthroline-based fluorescent sensor was designed and synthesized from optical active ß-amino acids. It used 1,10-phenanthroline moiety as a fluorescent signaling site and binding site, with optically active ß-amino acids as a chiral barrier site. Notably, the optically active ß-amino acids were obtained by a Lewis base catalyzed hydrosilylation of ß-enamino esters according to our former work. The chiral sensor has been used to conduct the enantioselective recognition of chiral mono and dicarboxylic acids derivatives. Using this fluorescent sensor, a moderate "turn-off" fluorescence-diminishment response towards enantiomer of tartaric acids, and proline was observed. It found that l-enantiomers quench the chiral fluorescence sensor more efficiently than d-enantiomers due to the absolute configuration of the ß-amino acid.

A novel dual-switch fluorescent probe for Cr(III) ion based on PET-FRET processes.

Two different strategies for photoinduced electron transfer (PET) and fluorescence resonance energy transfer (FRET) have been designed and combined into one sensing system. The novel probe NNRhB was developed based on 1,8-naphthalimide and rhodamine moieties, in which two fluorophores are sensitive to the presence of Cr(3+) in different chromium ion concentration regimens. Therefore, the proposed sensing system represents dual-switch states and segmented detection behavior, with the fluorescence emission color spans from green to orange over an increasing Cr(3+) concentration gradient. When excited in the visible region, the initial emission band at 537 nm was enhanced. That was attributed to the suppression of the PET process, which arose from Cr(3+)-coordination with a 1,8-naphthalimide derivative. At a sufficiently high concentration of Cr(3+) (over 9 µM), the spirolactam rhodamine component in NNRhB converted to the opened form as a result of Cr(3+) coordination, which turned the emission color from green to orange via FRET. The fluorescence phenomena of the compound 1 and compound 2 split from compound NNRhB confirm our hypothesis of the spectral response mechanisms. Moreover, compared with a single fluorescent response in compound 1 or compound 2, the dual-switch fluorescent probe NNRhB shows a more sensitive and distinct visual detection ability for Cr(3+) ions. This probe affords a high selectivity and sensitivity to Cr(3+) from 30 nM to 80 µM; the detection limit was 0.14 nM. The results of practical application experiments suggest that the Cr(3+)-selective ligand prepared here may provide an effective strategy for detection of Cr(3+) in environmental and biological applications.