Article
Chemistry, Organic
David A. Candito, Yingchun Ye, Ryan Quiroz, Michael H. Reutershan, David Witter, Surendra B. Gadamsetty, Hongming Li, Josep Sauri, Sebastian E. Schneider, Yu-hong Lam, Rachel L. Palte
Summary: This study presents a flexible and robust strategy for accessing tetrahydrofuro[3,4-b]furan nucleoside analogues in the context of a PRMT5 inhibitor program. Compound 1.1-C was synthesized and demonstrated to be a potent PRMT5 inhibitor, laying the groundwork for the development of new inhibitors and nucleoside chemical matter for drug discovery programs.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Hongfei Jiang, Wujun Chen, Jie Wang, Renshuai Zhang
Summary: Numerous strategies have been developed and applied in the field of biological chemistry to link desired chemical probes with target peptides and proteins. Site-specific modification of native amino acid residues provides novel biological tools for understanding the role of peptides and proteins. Selective N-terminal modification strategies, which have been extensively studied in the last decade, have the potential for applications in medicine, basic research, and applied materials science.
CHINESE CHEMICAL LETTERS
(2022)
Article
Biochemical Research Methods
Ying Cong, Paul D. Scesa, Eric W. Schmidt
Summary: A key goal of synthetic biology is to modify peptides and proteins through designed modifications, both inside and outside the cell. This study investigates a specific enzyme that can protect the ends of peptides, and shows that mutating the enzyme's active site can expand its substrate range, including reverse geranylation of peptide N-termini.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemical Research Methods
Ying Cong, Paul D. Scesa, Eric W. Schmidt
Summary: A key goal of synthetic biology is to enable the designed and modification of C-Terminal enzymes. AgeMTPT is a selective enzyme that protects the N-terminus of peptides and modifies the C-terminus through enzymatic reactions. The substrate selectivity of this enzyme requires N-terminal aromatic amino acids and tolerates diverse uncharged amino acids in other positions. Mutagenesis of the active site of AgeMTPT expands its substrate scope, including the reverse geranylation of peptide N-termini, revealing potential applications in synthetic biology.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Chemistry, Organic
Zhizhou Chen, Xiangwen Kong, Shengtong Niu, Shuang Yang, Jinggong Liu, Bolai Chen, Benlong Luo, Changyu Zhou, Chenglin Ding, Xinqiang Fang
Summary: Asymmetric construction of cyclopentenones using N-Heterocyclic carbene catalysis with enals and alpha-diketones has been achieved, yielding a series of highly functionalized cyclopentenones in a highly diastereo- and enantioselective manner. The protocol is tolerant of substrates with both aromatic and aliphatic groups, and further transformations of the products have led to a range of value-added molecules.
Article
Chemistry, Multidisciplinary
Jia-Dong Guo, Xiu-Long Yang, Bin Chen, Chen-Ho Tung, Li-Zhu Wu
Summary: By using a catalytic amount of N-iodosuccinimide (NIS) in combination with O-2 in air, a series of 10-phenanthrenols were efficiently and scalably constructed under sunlight at room temperature. Mechanistic studies revealed that H2O2 generated in situ was responsible for initiating the later catalytic cycle by converting I-2 to IOH.
Article
Chemistry, Multidisciplinary
Benjamin Emenike, Julia Donovan, Monika Raj
Summary: Protein α-N-terminal dimethylation is an underexplored posttranslational modification (PTM) with increasing implications in vital physiological and pathological processes. The lack of a pan-selective method for detecting α-N-terminal dimethylation hinders the identification of its sites in the proteome.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Ivan Volchkov, Brent V. Powell, Olga V. Zatolochnaya, Joyce C. Leung, Scott Pennino, Lifen Wu, Nina C. Gonnella, Bangaru Bhaskararao, Marisa C. Kozlowski, Jonathan T. Reeves
Summary: This article reports a practical method for the synthesis of di- and trisubstituted vinyl fluorides through a selective olefination/hydrolysis reaction. The method allows for the production of the desired compounds with high isomeric purity and without the need for tedious chromatography.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Chien- Yang, Jiwoo Kim, Shu-Ou Shan
Summary: The ribosome actively participates in diverse protein biogenesis pathways, including folding, localization, and modifications. It imposes an additional layer of substrate selection during N-terminal methionine excision (NME) in bacteria.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Krystal Diaz, Ying Meng, Rong Huang
Summary: The posttranslational methylation of the alpha-N-terminal amino group of proteins, first documented over 40 years ago, has been relatively less explored compared to lysine and arginine methylation. Increasing reports suggest that alpha-N-terminal methylation plays a widespread and critical regulatory role in mitosis, chromatin interactions, DNA repair, and translation fidelity. Recent advances include the understanding of biological functions and mechanisms, substrate recognition, discovery of inhibitors, and crosstalk with other N-terminal modifications.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Organic
Nuria Mazo, Imran R. Rahman, Claudio D. Navo, Jesus M. Peregrina, Jesus H. Busto, Wilfred A. . van der Donk, Gonzalo Jimenez-Oses
Summary: This study reports a common strategy for the synthesis of lanthionine derivatives using nucleophilic ring opening of cyclic sulfamidates derived from amino acids. The researchers achieved regio-, chemo-, and stereoselective intramolecular S-alkylation of a cysteine residue with N-sulfonyl sulfamidates for the synthesis of cyclic lanthionine-containing peptides. Four different analogues of cytolysin S (CylLS '') were successfully synthesized and their conformational preferences and biological activities were compared with wild-type CylLS ''.
Article
Chemistry, Organic
Bhaskar Chatterjee, Dhananjoy Mondal, Smritilekha Bera
Summary: Diaminopimelic acid and its analogues have been a focus of research for their synthesis and biological activities to explore their mechanism of action and antimicrobial potential. By comprehensively analyzing synthetic ventures and biological activities, a deeper understanding of the chemical and biological characteristics of these compounds can be gained.
Article
Chemistry, Organic
Narra Rajashekar Reddy, Shaik Gouse, Sudhagar Selvaraju, Sundarababu Baskaran
Summary: A facile domino strategy for the synthesis of biologically active cyclopent-2-enone core containing CA-4 analogues has been developed. The methodology involves a sequence of semipinacol rearrangement, iterative aldol condensation, and iso-Nazarov cyclization reactions. Enantioselective synthesis of S-hydroxy-cyclopent-2-enones using the Sharpless AD catalyst was also achieved. Biological studies showed better inhibitory activity against cell proliferation for (S)-enantiomers than (R)-enantiomers.
Article
Biochemical Research Methods
Panyue Chen, Tiago Jose Paschoal Sobreira, Mark C. Hall, Tony R. Hazbun
Summary: The study reanalyzed proteomic datasets to explore the extent of alpha-N-terminal methylation in yeast and humans, finding evidence of canonical and noncanonical sequences being methylated. A unique amino acid frequency pattern was observed for the methylated peptides in yeast and humans, differing from the canonical motif. This study demonstrates the feasibility of using proteomic data for global investigations into alpha-N-terminal methylation.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Christian Paul Bold, Melanie Gut, Jasmine Schurmann, Daniel Lucena-Agell, Jurg Gertsch, Jose Fernando Diaz, Karl-Heinz Altmann
Summary: The study describes the convergent synthesis of analogues of the marine macrolide (-)-zampanolide, incorporating an embedded N-substituted morpholine moiety. Among the three investigated morpholino-zampanolides, the N-acetyl and N-benzoyl derivatives both showed nanomolar antiproliferative activity, while the N-tosyl derivative had significantly reduced activity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Jiuling Li, Dong Xing, Wenhao Hu
Summary: An efficient synthesis method for alpha-halo-alpha-arylseleno ketones has been developed through gem-difunctionalization of alpha-diazoarylketones with diaryldiselenides and N-halosuccinimides. A series of products were obtained in excellent yields and chemoselectivities under mild conditions. The transformation is proposed to occur via the generation of a key intermediate arylselenenyl halide from diaryldiselenides/N-halosuccinimides, followed by addition with alpha-diazoarylketones to form the desired gem-difunctionalization products.
MOLECULAR DIVERSITY
(2021)
Article
Chemistry, Organic
Farrukh Sajjad, Alavala Gopi Krishna Reddy, Dong Xing, Suzhen Dong, Wenhao Hu
Summary: An unprecedented synthetic route towards a variety of 3-anilino-1H-indoles has been achieved through a domino ruthenium-catalyzed annulation and subsequent iron-promoted fragmentation and rearrangement. The strategy is applicable to deliver diversely substituted indole esters, with compound 4i exhibiting the best inhibitory activity with an IC50 value of 0.05 mu M, paving the way for the discovery of promising lead compounds in the future.
Article
Chemistry, Multidisciplinary
Guizhi Dong, Ming Bao, Xiongda Xie, Shikun Jia, Wenhao Hu, Xinfang Xu
Summary: The study presents an unprecedented catalytic asymmetric allylation of isatins and isatin-derived ketimines via a gold and chiral organocatalyst cooperative catalysis strategy, leading to the expeditious synthesis of chiral 2,5-disubstituted alkylideneoxazolines with vicinal stereogenic centers. The mechanism involves an alkylgold intermediate, and the X-ray crystal structure of the allylgold species reveals its unique stability and reactivity. Additionally, an asymmetric formal hetero-ene reaction of the gold intermediate is enabled with the assistance of a quinine-derived squaramide catalyst, extending the synthetic applications of gold complexes and the versatility of gold catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
G. Lakshma Reddy, Rupam Sarma, Shuhao Liu, Weifeng Huang, Jinping Lei, Jiasheng Fu, Wenhao Hu
Summary: This study describes the design and synthesis of novel benzo[4,5]imidazo[1,2-a]pyrazin-1-amine derivatives, which showed promising A(2A) adenosine receptor antagonist activity, with compound 27 demonstrating good activity and potential application in T-cell activation. Molecular docking studies were conducted to explain the observed binding affinity of compound 27.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Ming Bao, Jinzhou Chen, Chao Pei, Sujie Zhang, Jinping Lei, Wenhao Hu, Xinfang Xu
Summary: An unprecedented gold-catalyzed ketene C=O/C=C bifunctionalization method has been developed, initiated by gold-catalyzed Wolff rearrangement of diazoketone to form the ketene intermediate, followed by nucleophilic addition and terminated with two divergent cyclization processes. Depending on the nucleophiles used, different cyclization pathways are observed, leading to the formation of different products, providing a novel reaction pattern for the ketene dual functionalization.
SCIENCE CHINA-CHEMISTRY
(2021)
Article
Chemistry, Applied
Ming Bao, Xiongda Xie, Wenhao Hu, Xinfang Xu
Summary: A gold-catalyzed carbocyclization/C=N bond formation cascade reaction has been developed for the synthesis of polyfunctionalized 4-iminonaphthalenones and indenes in good to high yields under mild reaction conditions. The resulting products could be converted into multi-substituted 2-naphthol derivatives in high yields.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Physical
Kemiao Hong, Shanliang Dong, Xinxin Xu, Zhijing Zhang, Taoda Shi, Haoxuan Yuan, Xinfang Xu, Wenhao Hu
Summary: An enantioselective intermolecular Mannich-type interception of phenolic oxonium ylides with imines has been developed using cooperative catalysis with achiral dirhodium complex and chiral phosphoric acid. The synthesis of enantioenriched 2,2-disubstituted dihydrobenzofurans with good to high yield and high to excellent enantioselectivity under mild conditions was achieved. Preliminary antitumor activity study showed high anticancer potency of the reduction product 7 against human lung adenocarcinoma cells (A549 cells, IC50 = 9.13 mu M).
Article
Chemistry, Multidisciplinary
Zhenghui Kang, Wenju Chang, Xue Tian, Xiang Fu, Wenxuan Zhao, Xinfang Xu, Yong Liang, Wenhao Hu
Summary: The study presents a novel asymmetric allylation reaction through ternary cooperative catalysis, enabling the expedient access to chiral alpha,alpha-disubstituted ketones with high enantioselectivity. Experimental and computational studies have elucidated the mechanism and origin of enantioselectivity in this three-component reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Xiangrong Liu, Xue Tian, Jiawu Huang, Yu Qian, Xinfang Xu, Zhenghui Kang, Wenhao Hu
Summary: An enantioselective three-component reaction of alpha-propargylic-3-indolymethanol with diazoindolinone and alcohol has been achieved under the cocatalysis of Rh(II) and chiral phosphoric acid (CPA). The reaction proceeds through regio- and enantiospecific addition of an in situ formed oxonium ylide to the alpha-propargylic indole iminium ion, providing an efficient access to chiral propargylic indole derivatives with high yields and enantioselectivities.
Article
Chemistry, Physical
Yong-Liang Su, Geng-Xin Liu, Luca De Angelis, Ru He, Ammar Al-Sayyed, Kirk S. Schanze, Wen-Hao Hu, Huang Qiu, Michael P. Doyle
Summary: This study demonstrates the efficient generation of functionalized derivatives through photocatalyzed multicomponent reactions using nitrogen aromatic heterocycles, alkenes, and diazo compounds. The reaction shows high functional group tolerance and exacting regioselectivities. Mechanistic studies, including photophysical measurements, provide insights into this radical cascade reaction.
Article
Chemistry, Organic
Xiang Fu, Jie Tang, Ruyu Hua, Xiaoqian Li, Zhenghui Kang, Huang Qiu, Wenhao Hu
Summary: This study reports two DNA-compatible reactions with alkenes and diazo compounds, providing hydroalkylation and cyclopropanation products in moderate to excellent yields. These transformations not only offer new access to C(sp3)-C(sp3) bond formation in DELs with excellent functional group tolerance, but also represent practical ligation methods to introduce functionalized molecules into DNA.
Article
Chemistry, Organic
Su Zhou, Qianqian Liu, Ming Bao, Jie Huang, Junjian Wang, Wenhao Hu, Xinfang Xu
Summary: A new synthesis method for 2-indolyl indolone N-oxides via gold(i)-catalyzed cascade reaction of o-nitroalkynes with indoles has been developed, leading to highly efficient conversion into 2-indolylbenzoxazinone with strong blue fluorescence. The synthesized compounds were also evaluated for their antitumor activity in small cell lung cancer, with compounds 3d and 4s showing high anticancer potency against SCLC cells.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Kai Zhou, Ming Bao, Hongkai Sha, Guizhi Dong, Kemiao Hong, Xinfang Xu, Wenhao Hu
Summary: A Rh-catalyzed diastereoselective three-component reaction has been developed for the efficient synthesis of vicinal diamine derivatives with two tertiary stereocenters in high yields (75%->95%) and high to excellent diastereoselectivities. The generated product can be easily converted to free diamines via hydrolysis of the imine motif under mild conditions.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Farrukh Sajjad, Yanmei Chen, Xue Tian, Suzhen Dong, Alavala Gopi Krishna Reddy, Wenhao Hu, Dong Xing
Summary: An efficient strategy for the construction of 1,4-oxazines from simple alpha-amino ketones and diazo pyruvates catalyzed by RuCl3 was reported, showing promising anticancer activities towards HCT116. This transformation involves a tandem N-H insertion/cyclization sequence via an enol formation under mild reaction conditions with broad functional group tolerance.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Jiuling Li, Bin Li, Juan Chen, Xinyu Jia, Min Wang, Chengjun Hao, Xinhua Zheng, Hongmei Dai, Wenhao Hu
Summary: A series of gem-chlorosulfurization products bearing difluoromethyl substituents were synthesized directly from p-toluenesulfonyl difluorodiazoethane (TsCF2CHN2), disulfides, and PhICl2 in high to excellent yields without the need for any catalysts or additives. The products showed high functional group compatibility and could be efficiently converted to sulfur-containing and aryl substituted difluoromethyl derivatives through a feasible multi-component operation.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
