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1.
Chem Soc Rev ; 52(7): 2358-2376, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-36916421

ABSTRACT

Copper-catalyzed enantioselective coupling has been widely investigated, which allows rapid construction of various chiral molecules. Despite important advances via polar and radical mechanisms, exploring general and practical strategies for the regio-, enantio- and diastereoselective assembly of stereogenic centers is of significant value but remains highly problematic. The integration of photocatalysis with asymmetric copper catalysis could provide appealing access to the development of new reaction pathways and structurally diverse chiral compounds, and extend the boundaries of radical chemistry. This review summarizes recent advances in photoinduced copper-catalyzed enantioselective coupling reactions, and discusses the mechanistic aspects.

2.
Molecules ; 29(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38792039

ABSTRACT

Camptothecin and its analogues show important antitumor activity and have been used in clinical studies. However, hydrolysis of lactone in the E ring seriously attenuates the antitumor activity. To change this situation, aromathecin alkaloids are investigated in order to replace camptothecins. Potential antitumor activity has obtained more and more attention from organic and pharmaceutical chemists. As a member of the aromathecin alkaloids, rosettacin has been synthesized via different methods. This review summarizes recent advances in the synthesis of rosettacin.

3.
Chem Rec ; 23(3): e202200255, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36646518

ABSTRACT

The isoindolo[2,1-b]isoquinolin-5(7H)-one scaffold is widely present in lots of bioactive natural products. Diverse types of strategies have been developed to construct this scaffold. Recently, transition metal-catalyzed C-H activation/annulation is emerging as a powerful and straightforward method to construct diverse polyheterocycles with high atom- and step-economy. It also has been employed for the synthesis of the isoindolo[2,1-b]isoquinolin-5(7H)-one scaffold. This review provides an introduction to recent advances for the preparation of isoindolo[2,1-b]isoquinolin-5(7H)-ones by using transition metal-catalyzed C-H activation/annulation. It will help researchers to find hidden opportunities and accelerate the discovery of novel transformations based on C-H activation/annulation.

4.
Chem Rec ; 23(10): e202300095, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37218998

ABSTRACT

The Ugi reaction has become one of the highly explored reactions for the formation of multifunctional adducts, due to the mild reaction conditions, wide scope and high variability. By carefully selecting the starting four components, Ugi-adducts could undergo different kinds of post-transformations for the synthesis of bioactive heterocycles, natural products and macrocycles. Considering the significance of polycycles, diverse post-Ugi transformations have been developed over the years for constructing structurally novel polycycles. In this account, we summarize important efforts for the synthesis of polycyclic N-heterocycles via post-Ugi cyclizations from the Van der Eycken laboratory onwards 2016. With the aid of transition metal catalysis from gold, rhodium, silver and palladium, as well as metal-free strategies, versatile polyheterocycles are prepared with high efficiency and step-economy.

5.
Angew Chem Int Ed Engl ; 62(33): e202305510, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37329214

ABSTRACT

Transition metal-catalyzed C-S cross-coupling has emerged as an important strategy to furnish thioethers; however, the dominant utilization of noble metal catalysts as well as the construction of challenging C(sp3 )-S bonds by transition metal-catalysis remain highly problematic. Earth-abundant manganese has gathered increasing interest as an attractive catalyst for new reaction development; nevertheless, C(sp3 )-S cross-coupling reaction by manganese catalysis has not been reported. Herein, we disclose a highly efficient manganese-catalyzed redox-neutral thiolation of a broad range of alkyl halides with thioformates as practical sulfuration agents. Strategically, employing easily synthesized thioformates as thiyl radical precursors allows access to various aryl and alkyl thioethers in good to excellent yields. Notably, this redox-neutral method avoids the utilization of strong bases, external ligands, forcing reaction conditions, and stoichiometric manganese, thus presenting apparent advantages, such as broad substrate scope, excellent functional group compatibility, and mild reaction conditions. Finally, the utilities of this method are also illustrated by downstream transformations and late-stage thiolation of structurally complex natural products and pharmaceuticals.

6.
Angew Chem Int Ed Engl ; 62(13): e202218286, 2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36719253

ABSTRACT

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

7.
Molecules ; 27(10)2022 May 12.
Article in English | MEDLINE | ID: mdl-35630582

ABSTRACT

Microwave irradiation and post-Ugi reactions own their respective advantages in comparison with other strategies. The combination of microwave irradiation and post-Ugi reactions shows paramount importance in the construction of polycycles. This minireview outlines the recent developments of microwave-assisted post-Ugi reactions for the synthesis of polycycles. Through transition metal-catalyzed or transition metal-free transformations, diverse polycycles are prepared in an efficient, rapid, and step-economical manner.


Subject(s)
Microwaves
8.
Chemistry ; 27(1): 121-144, 2021 Jan 04.
Article in English | MEDLINE | ID: mdl-32530508

ABSTRACT

Polycycles are abundantly present in numerous advanced chemicals, functional materials, bioactive molecules and natural products. However, the strategies for the synthesis of polycycles are limited to classical reactions and transition metal-catalyzed cross-coupling reactions, requiring pre-functionalized starting materials and lengthy synthetic operations. The emergence of novel approaches shows great promise for the fields of organic/medicinal/materials chemistry. Among them, transition metal-catalyzed C-H activation followed by intermolecular annulation reactions prevail, due to their straightforward manner with high atom- and step-economy, providing rapid, concise and efficient methods for the construction of diverse polycycles. Several strategies have been developed for the synthesis of polycycles, relying on sequential multiple C-H activation/annulation, or combination of C-H activation/annulation and further interaction with a proximal group, or merger of C-H activation with a cycloaddition reaction, or in situ formation of the directing group. These are attractive, efficient, step- and atom-economic methods starting from commercially available materials. This Minireview will provide an introduction to transition metal-catalyzed C-H activation for the synthesis of polycycles, helping researchers to discover indirect connections and reveal hidden opportunities. It will also promote the discovery of novel synthetic strategies relying on C-H activation.

9.
Org Biomol Chem ; 19(44): 9752-9757, 2021 11 18.
Article in English | MEDLINE | ID: mdl-34730164

ABSTRACT

A palladium-catalyzed intramolecular cyclization of Ugi-adducts via a cascade dearomatization/aza-Michael addition process has been developed. Diverse plicamine analogues are constructed in a rapid, highly efficient and step-economical manner, through the combination of an Ugi-4CR and a palladium-catalyzed dearomatization. The synthetic utility of this approach is illustrated by further functional group transformations.

10.
J Org Chem ; 85(12): 8045-8054, 2020 06 19.
Article in English | MEDLINE | ID: mdl-32441517

ABSTRACT

A pyridine-enabled C-N bond activation of peptidomimetics employing cooperative palladium/copper catalysis in water is developed. Diverse amides and 4-pyridylglyoxamides are simultaneously synthesized through two steps from commercially available materials in a rapid, environmentally friendly, and high atom-economical manner.

11.
J Org Chem ; 85(23): 15092-15103, 2020 12 04.
Article in English | MEDLINE | ID: mdl-33200934

ABSTRACT

The development of a rapid and diverse access to complex natural product-like 3,4-fused indole scaffolds has always attracted considerable attention from synthetic and medicinal communities. We herein disclose a modular and straightforward protocol to prepare the densely substituted polycyclic azepino[5,4,3-cd]indole scaffolds. This synthetic process involves an Ugi four-component reaction from easily available starting materials and a gold-catalyzed post-Ugi domino dearomatization/Michael addition sequence, enabling facile access to the highly functionalized azepino[5,4,3-cd]indole core with excellent chemo-, regio-, and diastereoselectivity.

12.
Chemistry ; 25(32): 7645-7648, 2019 Jun 07.
Article in English | MEDLINE | ID: mdl-31017698

ABSTRACT

A catalyst-controlled intramolecular carbocyclization of 2-alkynyl aryl ketones is presented. Under rhodium(III) catalysis, 1-indanones are formed through 5-exo-dig carbocyclizations with exclusive chemo-, regio- and stereoselectivity. When catalyzed by copper(I), 1-naphthols are obtained through 6-endo-dig carbocyclizations with exclusive chemo- and regioselectivity.

13.
Beilstein J Org Chem ; 15: 571-576, 2019.
Article in English | MEDLINE | ID: mdl-30873242

ABSTRACT

A rhodium(III)-catalyzed intramolecular oxidative annulation of O-substituted N-hydroxyacrylamides for the construction of indolizinones via sequential C(sp2)-H activation and C(sp3)-H amination has been developed. This approach shows excellent functional-group tolerance. The synthesized scaffold forms the core of many natural products with pharmacological relevance.

14.
Med Phys ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016559

ABSTRACT

BACKGROUND: X-ray radiography is a widely used imaging technique worldwide, and its image quality directly affects diagnostic accuracy. Therefore, X-ray image quality control (QC) is essential. However, subjectively assessing image quality is inefficient and inconsistent, especially when large amounts of image data are being evaluated. Thus, subjective assessment cannot meet current QC needs. PURPOSE: To meet current QC needs and improve the efficiency of image quality assessment, a complete set of quality assessment criteria must be established and implemented using artificial intelligence (AI) technology. Therefore, we proposed a multi-criteria AI system for automatically assessing the image quality of knee radiographs. METHODS: A knee radiograph QC knowledge graph containing 16 "acquisition technique" labels representing 16 image quality defects and five "clarity" labels representing five grades of clarity were developed. Ten radiographic technologists conducted three rounds of QC based on this graph. The single-person QC results were denoted as QC1 and QC2, and the multi-person QC results were denoted as QC3. Each technologist labeled each image only once. The ResNet model structure was then used to simultaneously perform classification (detection of image quality defects) and regression (output of a clarity score) tasks to construct an image QC system. The QC3 results, comprising 4324 anteroposterior and lateral knee radiographs, were used for model training (70% of the images), validation (10%), and testing (20%). The 865 test set data were used to evaluate the effectiveness of the AI model, and an AI QC result, QC4, was automatically generated by the model after training. Finally, using a double-blind method, the senior QC expert reviewed the final QC results of the test set with reference to the results QC3 and QC4 and used them as a reference standard to evaluate the performance of the model. The precision and mean absolute error (MAE) were used to evaluate the quality of all the labels in relation to the reference standard. RESULTS: For the 16 "acquisition technique" features, QC4 exhibited the highest weighted average precision (98.42% ± 0.81%), followed by QC3 (91.39% ± 1.35%), QC2 (87.84% ± 1.68%), and QC1 (87.35% ± 1.71%). For the image clarity features, the MAEs between QC1, QC2, QC3, and QC4 and the reference standard were 0.508 ± 0.021, 0.475 ± 0.019, 0.237 ± 0.016, and 0.303 ± 0.018, respectively. CONCLUSIONS: The experimental results show that our automated quality assessment system performed well in classifying the acquisition technique used for knee radiographs. The image clarity quality evaluation accuracy of the model must be further improved but is generally close to that of radiographic technologists. Intelligent QC methods using knowledge graphs and convolutional neural networks have the potential for clinical applications.

15.
Front Pharmacol ; 15: 1367682, 2024.
Article in English | MEDLINE | ID: mdl-38500766

ABSTRACT

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation. Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel. Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine. Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

16.
Org Lett ; 25(17): 2996-3000, 2023 05 05.
Article in English | MEDLINE | ID: mdl-37129283

ABSTRACT

Herein, we disclose a Rh(III)-catalyzed C-H activation/annulation reaction for the derivatization of Lys-based peptides, in situ affording diverse peptide-isoquinolone conjugates. This approach features racemization-free conditions, high atom- and step-economy, excellent chemo- and site-selectivity, and broad scope including substrates bearing unprotected Trp and Tyr, free Ser and Gln, and Met residues. The peptide-isoquinolone conjugates also display good fluorescent properties with maximum emission wavelengths up to 460 nm. Importantly, preliminary antifungal activity studies indicate that peptide-isoquinolone conjugates show potential activities toward crop and forest pathogenic fungi, in which the peptide-isoquinolone conjugate bearing unprotected Tyr residue exhibits much better antifungal activities toward B. cinerea Pers. and C. chrysosperma than the positive control.


Subject(s)
Antifungal Agents , Peptides , Antifungal Agents/pharmacology , Fungi , Catalysis
17.
Nat Commun ; 14(1): 4261, 2023 07 17.
Article in English | MEDLINE | ID: mdl-37460623

ABSTRACT

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.


Subject(s)
Acute Kidney Injury , Kidney , Animals , Male , Mice , Acute Kidney Injury/metabolism , Apoptosis , Cisplatin/adverse effects , Kidney/metabolism , Kidney Tubules/metabolism , Mice, Inbred C57BL , Receptors, TNF-Related Apoptosis-Inducing Ligand
18.
Nat Commun ; 13(1): 7450, 2022 12 02.
Article in English | MEDLINE | ID: mdl-36460657

ABSTRACT

Alcohols are ubiquitous in chemistry and are native functionalities in many natural products and bioactive molecules. As such, a strategy that utilizes hydroxy-containing compounds to develop bond disconnection and bond formation process would achieve molecular diversity. Herein we utilize bench-stable N-alkoxyphthalimides prepared from alcohols to couple with glycine derivatives via radical process under visible light irradiation, providing a variety of unnatural amino acid (UAA) and peptide derivatives. The approach allows to rapidly deconstruct molecular complexity via ß-fragmentation such as saclareolide, ß-pinene and camphor and provides products with unique scaffolds, which show inhibition toward the pathogenic fungi growth.


Subject(s)
Biological Products , Fabaceae , Amino Acids , Camphor , Glycine
19.
Org Lett ; 24(5): 1232-1236, 2022 Feb 11.
Article in English | MEDLINE | ID: mdl-35099981

ABSTRACT

A palladium-catalyzed reaction of N-propargyl oxazolidines with alkenes for the synthesis of indolizidines has been developed. Through a sequential 6-exo-dig cyclization/proton transfer/[3+2] cycloaddition/cycloreversion/aromatization process, a series of fused polycyclic indolizines are obtained in moderate to good yields with high functional group tolerance. Experimental and theoretical studies suggest that the [3+2] cycloaddition/cycloreversion of the oxazolidine ring probably involves C-C and C-O bond cleavage, providing a new ring restructuring approach for the synthesis of heterocycles.

20.
Org Lett ; 24(46): 8536-8541, 2022 11 25.
Article in English | MEDLINE | ID: mdl-36374298

ABSTRACT

A gold(I)-catalyzed cascade intramolecular cyclization of Ugi adducts for the divergent construction of quinazolinone and ampakine analogues has been developed in a rapid, highly efficient and step-economical manner. This protocol shows high yields, excellent functional-group tolerance, broad substrate scope and excellent chemo- and regioselectivity. The practicality of this strategy is further demonstrated by a scale-up reaction. Diverse oligopeptides are also found to be well tolerated, affording polycyclic products decorated with a peptide chain.


Subject(s)
Gold , Quinazolinones , Gold/chemistry , Catalysis , Cyclization
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