Copper-Catalyzed Oxidative [3 + 2] Cycloaddition of Enamines and Pyridotriazoles toward Indolizines.

An efficient copper catalytic system has been established for the synthesis of highly functional indolizines through oxidative [3 + 2] cycloaddition of enamines and pyridotriazoles. This modular platform is compatible with a broad range of functional groups, including natural and complex skeletons, allowing for late-stage modifications. It features a step-economical, highly regioselective, and easy-handling procedure and has been applied in constructing small molecules of potent activity toward inhibiting the VEGF-NRP1 interaction through a one-pot reaction of pyridotriazoles, amines, and aldehydes.

Amine-Release Annulation of Enaminones: Bimetallic Co-Catalytic Synthesis of Cyclopentadienes from Alkynes.

An efficient Au(III)/Ag(I) co-catalytic platform has been established for the synthesis of cyclopentadienes through amine-release annulation of enaminones with alkynes. Vinylcarbenoids that were generated from 1,2-migration of propargyl esters may undergo a tandem annulation process with enaminones to give aminocyclopentenes as key intermediates. The bimetal catalytic system is compatible with a broad substrate scope under mild reaction conditions. The obtained cyclopentadienes are allowed to undergo late-stage modifications into complex molecules with high chemo- and regioselectivities.

Modular synthesis of fluorinated 2H-thiophenes via [4 + 1] cyclization of enaminothiones.

An efficient and straightforward synthetic method for constructing trifluoromethyl 2H-thiophenes through [4 + 1] cycloaddition of enaminothiones with trifluoromethyl N-tosylhydrazones has been disclosed. The cycloaddition platforms were found to be compatible with a broad substrate scope and to show high regio- and stereo-selectivities under very mild reaction conditions such as room temperature, neutral media and low loading of catalyst.

Metal-free synthesis of ß-aminoketones by the reductive hydroamination of ynones.

This study describes a cascade method for the synthesis of ß-aminoketones through the reductive hydroamination of alkynes under very mild metal-free conditions. It allows for the rapid conversion of ynones and amines into corresponding ß-aminoketones with a broad substrate scope and diverse functionalities. This straightforward and easy-to-handle reaction process can be successfully applied for the synthesis of Proroxan and Propipocaine, offering a potential option for the synthesis of drug molecules with the ß-aminoketone skeleton.

Metal-free synthesis of gem-difluorinated heterocycles from enaminones and difluorocarbene precursors.

A cascade strategy to synthesise gem-difluorinated 2H-furans from reactions of BrCF2CO2Et with enaminones has been described. The reactions tolerate a wide variety of functional groups under metal-free conditions. An active aminocyclopropane is proposed to be a key intermediate through the cyclopropanation of difluorocarbene with enaminones, which further triggers a regioselective C-C bond cleavage in situ to afford the corresponding gem-difluorinated 2H-furans.

Palladium-Catalyzed Decarbonylation of Amino Acid Derivatives via C-C Bond and C-N Bond Dual Activations.

A unique decarbonylation of an amino acid derivative catalytic system has been established via palladium-catalyzed C-C bond and C-N bond dual activations. By employing 8-aminoquinoline as the directing group, this transformation has been found to facilitate the high chemoselectivity to decarbonylation of amino acid derivatives rather than intramolecular deamination or cross-dehydrogenative coupling reactions. This method provides a straightforward avenue for constructing diverse functionalized amide compounds in good to excellent yields. We proposed a possible reaction pathway that may go through the C-C bond and C-N bond dual activations on the basis of the mechanistic studies.

An expedient synthesis of highly functionalized 1,3-dienes by employing cyclopropenes as C4 units.

An efficient method has been described to synthesize dicarbonyl functionalized 1,3-dienes by cleaving the C[double bond, length as m-dash]C bond of enaminones with cyclopropenes in the presence of a rhodium catalyst. The acetate-substituted cyclopropenes are judiciously chosen as standard C4 units of 1,3-diene precursors. The reactions are believed to undergo a unique cutting and insertion process, involving a C[double bond, length as m-dash]C bond cleavage of the enaminone and insertion of a new C(sp2) source with the formation of two C-C single bonds. A broad range of substrates can be used to synthesize the corresponding 1,3-dienes under very mild reaction conditions, including low catalyst-loading, ambient temperature, and a neutral reaction solvent.

A protocol of systematic review and meta-analysis of acupuncture for drug resistant epilepsy.

BACKGROUND: This study aims to appraise the effectiveness and safety of acupuncture for drug resistant epilepsy (DRE). METHODS: We will search all potential randomized controlled trials (RCTs) of acupuncture for patients with DRE from their origin to March 1, 2020: MEDLINE, EMBASE, Cochrane Library, CINAHL, Scopus, WANGFANG, and Chinese Biomedical Literature Database. We will not apply any restrictions to the language and publication date. All RCTs investigating the effectiveness and safety of acupuncture for patients with DRE will be included. Study quality will be appraised by Cochrane risk of bias, and statistical analysis will be scrutinized by RevMan 5.3 software. Whenever possible, a narrative summary to describe study quality and content of the evidence will be performed. RESULTS: This study will provide summarize high quality evidence and will utilize a variety of outcome measurements to verify effectiveness and safety of acupuncture for DRE. CONCLUSION: The results of this study will seek to explore the effectiveness and safety of acupuncture for DRE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020170517.

Stereoselective Synthesis of Vinylcyclopropa[b]indolines via a Rh-Migration Strategy.

A mild rhodium catalytic system has been developed to synthesize vinylcyclopropa[b]indolines through cyclopropanation of indoles with vinyl carbenoids generated from ring opening of cyclopropenes in situ. By employing a Rh-migration strategy, the products can be obtained with good to excellent E:Z ratios (≤99:1) and complete diastereoselectivity (≤99:1). This method is easy, has a low catalyst loading, and works for a broad range of functionalities.

Can Botulinum Toxin Type A effectively treat neuropathic pain in spinal cord injury?: A protocol of systematic review and meta-analysis.

BACKGROUND: This protocol aims to assess the efficacy and safety of Botulinum Toxin Type A (BTTA) for the treatment of neuropathic pain (NPP) in patients with spinal cord injury (SCI). METHODS: We will retrieve databases in Cochrane Library, EMBASE, MEDLINE, Excerpta Medica Database, PsychINFO, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the beginning to the March 1, 2020. We will consider any potential studies on assessing the efficacy and safety of BTTA for the treatment of NPP in patients with SCI without limitations of language and publication status. Cochrane risk of bias will be used to assess the risk of bias for all included trials. RevMan 5.3 software will be utilized to synthesize the extracted data and to analyze those data. RESULTS: This study will appraise the efficacy and safety based on the current evidence of BTTA for the treatment of NPP in patients with SCI. CONCLUSION: This study will exert high quality clinical trials for exploring the efficacy and safety of BTTA in treating NPP in patients with SCI. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020170474.

Association between serum lipoprotein levels and cognitive impairment in acute cerebral infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: The objective of this study is to examine the association between serum lipoprotein levels (SLL) and cognitive impairment (CI) in patients with acute cerebral infarction (ACI). METHODS: All published studies will be searched from the following electronic databases: PubMed, EMBASE, Cochrane Library, PsycINFO, Web of Science, WANGFANG, and China National Knowledge Infrastructure from inauguration of each electronic database up to March 1, 2020. In addition, we will also search other sources, such as dissertations, Google scholar, conference proceedings, and reference lists of relevant reviews. We will not apply any language restrictions to the electronic databases. Two researchers will independently carry out literature selection, data collection, and methodological quality. A third researcher will help to solve any divergences by discussion. The RevMan 5.3 software will be employed to pool the collected data and to analyze the outcome data. RESULTS: This study will scrutinize the association between SLL and CI in patients with ACI. CONCLUSIONS: The results of this study will present helpful evidence of the association between SLL and CI in patients with ACI.Registration number: INPLASY202040018.

Association between serum lipoprotein levels and neurological function in patients with acute ischemic stroke: A protocol of systematic review and meta-analysis.

BACKGROUND: The target of this study is to summarize the association between the serum lipoprotein levels and neurological function in patients with acute ischemic stroke. METHODS: A comprehensive search of Cochrane Library, PUBMED, EMBASE, Web of Science, and Chinese Biomedical Literature Database, China National Knowledge Infrastructure from inception to the February 29, 2020 without language and publication date restrictions. All searched studies will be selected by 2 authors independently against the eligibility criteria. Included studies will be critically appraised, and essential data will be extracted by 2 independent authors. If necessary, meta-analysis will be utilized to synthesize the outcome data from included articles. If it is not possible, a narrative synthesis will be undertaken. RESULTS: This study will summarize the up-to-date evidence to investigate the association between serum lipoprotein levels and neurological function in patients with acute ischemic stroke. CONCLUSION: Its results may present beneficial evidence and guidance for the clinical practice and further studies. STUDY REGISTRATION NUMBER: INPLASY202040043.

Copper-Catalyzed Functionalization of Aza-Aromatic Rings with Fluoroalcohols via Direct C(sp2)-H/C(sp3)-H Coupling Reactions.

An efficient copper-catalyzed direct C(sp2)-H/C(sp3)-H coupling reaction of aza-aromatic rings with fluoroalcohols is developed. A variety of useful building blocks including hydroxyfluoroalkylated aniline, pyrrole, and indole derivatives bearing a quaternary carbon center could be constructed with high regioselectivity and good to excellent yields under very mild reaction conditions. The reaction is believed to undergo a fluoroalcohol oxidation and to follow an electronic addition reaction pathway.

2H-Azirines as Potential Bifunctional Chemical Linkers of Cysteine Residues in Bioconjugate Technology.

2H-Azirine-2-caboxamides have been designed to perform as a new type of bifunctional thiol linker under very mild reaction conditions. The cleavage of a C-N double bond of 2H-azirine furnishes an amino amide functional group in situ through a thiol addition and ring-opening process. It works with a broad scope of thiols and 2H-azirines in the absence of any catalysts at room temperature. Cysteine-containing peptides have also been demonstrated to work efficiently in a completely water solution.

Stereoselective synthesis of trifluoromethyl-substituted 2H-furan-amines from enaminones.

A straightforward strategy for synthesis of highly functionalized trifluoromethyl 2H-furans is described. The copper catalyzed method relies on a cascade cyclic reaction between enaminones and N-tosylhydrazones. This method allows the synthesis of 2-amino-3-trifluoromethyl-substituted 2H-furan derivatives carrying a quaternary stereogenic center as single diastereomers. The proposed reaction mechanism involves an amino-cyclopropane intermediate formed in the cyclopropanation of enaminones. The developed method tolerates a broad spectrum of functionalities, and the obtained 2H-furan derivatives are useful synthetic intermediates for preparing other trifluoromethyl-substituted compounds.

Synthesis of Functionalized α-Vinyl Aldehydes from Enaminones.

An efficient RhII -catalyzed synthesis of functionalized α-vinyl aldehydes with high E/Z stereoselectivity was developed. The reaction mediates the cyclopropanation of enaminones with vinyl carbenoids that are generated from cyclopropenes in situ to give the aminocyclopropane intermediates. Selective C-C bond cleavage of the cyclopropane intermediates leads to formation of α-vinyl aldehyde derivatives with high E/Z selectivity. This method proceeds at room temperature under very mild reaction conditions and works with a broad substrate scope.

Reactions of 5-Aminoisoxazoles with α-Diazocarbonyl Compounds: Wolff Rearrangement vs N-H Insertion.

A highly chemoselective reaction between 5-aminoisoxazoles and α-diazocarbonyl compounds has been described. Both Wolff rearrangement and N-H insertion products can be obtained selectively by the judicious choice of reaction conditions. In the case of the Wolff rearrangement reactions, the N-isoxazole amides are accessed as the sole products under thermal conditions. On the other hand, α-amino acid derivatives of N-isoxazolescan be obtained through N-H insertion reactions in the presence of catalytic Rh2(Oct)4. Both reactions proceed under mild reaction conditions and feature a broad substrate scope.

Synthesis of Polyaromatic Rings: Rh(III)-Catalyzed [5 + 1] Annulation of Enaminones with Vinyl Esters through C-H Bond Functionalization.

An expedient [5 + 1] annulation method via Rh(III)-catalyzed C-H bond functionalization of enaminones to synthesize polyaromatic rings is described. The reaction tolerates a broad range of functional groups and offers a new entry to construct polycyclic aromatic compounds with amino and formyl substituents. A possible reaction mechanism was proposed based on the results obtained from isotope labeling experiments.

Hoveyda-Grubbs II Catalyst: A Useful Catalyst for One-Pot Visible-Light-Promoted Ring Contraction and Olefin Metathesis Reactions.

A one-pot reaction to synthesize functionalized 2 H-azirines through visible-light-mediated ring contraction and olefin metathesis of isoxazoles is described. Hoveyda-Grubbs II catalyst was found to function as a photocatalyst for these transformations, allowing these processes to be carried out in a one-pot manner. This study offers a new entry for the application of Grubbs catalysts as efficient photocatalysts and the possibilities of carrying out other photoreactions and olefin metathesis in a one-pot process.

Highly Site-Selective Metal-Free C-H Acyloxylation of Stable Enamines.

A highly site-selective acyloxylation of stable enamines with PhI(OAc)2 under metal-free conditions to afford (E)-vinyl acetate derivatives in good to excellent yields is described. Depending on the judicious choice of the solvent system, either the α- or ß-site-selective product could be obtained with high selectivity. For the α-site-selective product, the rearranged amide compound is obtained as the major product. This reaction proceeds under mild reaction conditions (room temperature, metal-free, and open-flask) and features a broad substrate scope.