TETRAHEDRON
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2017
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IF 2.651
Yanmin Yao,Xiaobin Wang,Guangxin Liang
We report concise asymmetric total syntheses of tetracyclic marine alkaloids (+)-agelastatin A and (+)-agelastatin B using a cationic cyclization-based approach, which features straightforward transformations with cost-effective chemicals and reagents.
研究领域:
有机化学
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药物化学
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DOI
高影响因子
JOURNAL OF NATURAL PRODUCTS
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2025
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IF 3.6
Zhenzhen Zhang,Wei Li,Miaomiao Chai,Bing Wang,Xiaomin Zhang,Dehai Li,Xueqian He,Zhenhui Wang
The first total synthesis of (±)-talaroenamine B was achieved through a concise four-step procedure. The key feature of this synthetic strategy lies in a one-pot reaction involving I (III)-mediated oxidative dearomatization to construct a racemic cyclohexanedione unit, followed by imination using a chiral auxiliary to afford a separable mixture of diastereoisomers. A further acid-catalyzed substitution reaction of aniline with the diastereoisomers led to the natural product (−)-talaroenamine B and its enantiomer (+)-talaroenamine B. Additionally, virtual screening was utilized to expand the chemo-diversity of talaroenamines, and (±)-talaroenamine B diphenylene derivatives 6–11 were obtained by replacing aniline with selected aniline derivatives in the final step of synthesis. The structures of the synthetic compounds were elucidated using NMR, HRESIMS, and electronic circular dichroism (ECD) data. Compound 6b displayed an acetylcholinesterase (AChE) inhibitory effect with an IC50 value of 4.5 μM, as well as cytotoxicity against the K562 cell line with an IC50 value of 5.6 μM.
研究领域:
有机化学
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药物化学
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生物化学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Liao Xuemei,Cheng Xin,Zhuang Ruirong,Zhou Beidou
The total synthesis of compound 1 , a chiral diglyceride metabolite present in both humans and fungi, was achieved via a seven-step route, affording the target molecule in 2.33% overall yield. The synthetic strategy involved: (1) selective protection of the terminal hydroxyl group of chiral ketal 2 with a sterically hindered benzyl group, followed by ketal deprotection to yield benzyl ether 4 ; (2) protection of the terminal hydroxyl group of benzyl ether 4 with a bulky silyl protecting group, and subsequent esterification of the remaining hydroxyl with erucic acid to generate ester 6 ; (3) removal of the silyl protecting group from ester 6 , followed by esterification of the liberated hydroxyl group with pentadecanoic acid to afford ester 8 ; and (4) selective deprotection of the benzyl group of ester 8 to furnish compound 1 . Network pharmacology and molecular docking studies identified 196 potential targets of compound 1 , with AKT1, ALB, CASP3, EGFR, HSP90AA1, IGF1, and SRC highlighted as potential hub targets. In silico analysis suggested potential therapeutic applications in diabetes, neuro-systemic diseases, thyroid hormone disorders, lipid disorders, tumors, and gynaecological diseases. Furthermore, in silico screening using three databases identified 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) as a potential biological target. However, in vitro HMGCR inhibition assays failed to demonstrate a significant reduction in cholesterol levels in human blood upon treatment with compound 1 . These findings contribute to the understanding of the chemical synthesis and biological activity of chiral diglycerides and provide a basis for future research in this area.
研究领域:
有机化学
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药物化学
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药理学
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生物化学
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计算生物学
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代谢性疾病
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癌症研究
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DOI
PubMed
高影响因子
Antibiotics-Basel
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2019
·Vol. 8
·期 2
·45
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IF 2.921
Bernardo Ribeiro da Cunha,Luís P. Fonseca,Cecília R. C. Calado
Given the increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures—platforms—that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines. During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.Keywords:antibiotic discovery platforms;drug screening;semi-synthesis;fully synthetic antibiotics;genomics;proteomics;metabolomics;lipidomics;metagenomics
研究领域:
药理学
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微生物学
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基因组学
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生物信息学
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DOI
PubMed
高影响因子
POWDER TECHNOLOGY
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2025
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IF 4.6
Danjiao Zhao,Yu Wang,Weiwei Guan,Hua Jiang,Youheng Wang,Xianjun Hou
Eco-friendly lubricant additives play a pivotal role in saving energy and advancing sustainable development. Focusing on the tribological properties of biomass-derived carbon microspheres (CSs), this study successfully synthesized by a one-step glucose hydrothermal method and systematically evaluated as lubricant additives in water-based polyethylene glycol (PEG400), non-polar polyalphaolefin base oil (PAO6), and commercial full synthetic motor oil (0 W-20). Results demonstrate that CSs exhibit excellent dispersion stability and significant friction-reduction and anti-wear effects in all three lubricants. Specifically, CSs maintained colloidal stability for 180 days in PEG400, achieved a maximum 32.7 % friction coefficient reduction in 0 W-20, and a maximum wear volume decrease of 65.6 % in PAO6. Analysis indicates that the excellent lubrication performance is mainly ascribed to the enhanced interfacial adhesion force derived from improved wettability, which contributes to the rapid formation of homogeneous adsorption oil films at the sliding interface. Simultaneously, the nanobearing effect generated by the spherical structure of CSs and the friction-induced formation of Fe₃O₄/CS composite films synergistically interact to achieve high-efficiency lubrication. This study systematically evaluates the application potential of CSs in both polar and non-polar lubricant systems, providing valuable insights for the future development of high-performance lubricants.
研究领域:
材料科学
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机械工程
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摩擦学
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可持续能源
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纳米技术
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产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
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IF 14.7
Cheng Min-Jing,Wu Yan-Yi,Zeng Hao,Zhang Tian-Hong,Hu Yan-Xia,Liu Shi-Yi,Cui Rui-Qin,Hu Chun-Xia,Zou Quan-Ming,Li Chuang-Chuang,Ye Wen-Cai,Huang Wei,Wang Lei
The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus . Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro -hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus . This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.
研究领域:
有机化学
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药物化学
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微生物学
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药学
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
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2023
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IF 4.1
Qichang Liu,Mei Zuo,Yi Song,Shuzhong He,Jian Huang,Yang Chen
BACKGROUND Phytopathogens cause various diseases by parasitizing crops, reducing crop yield and resulting in substantial economic losses in agricultural production. A novel type isolated from the perennial herbaceous Peganum harmala L. seeds, β -carboline alkaloids pegaharine A ( PA ), has become a hot topic in developing plant-originated green pesticides owing to their significant physiological activities. RESULTS A scalable bioinspired total synthesis of PA is accomplished in the present work. The systematical biological assay study showed that PA exhibited moderate inhibitory activity against nine tested plant pathogenic fungi and showed significant inhibitory activity in vitro against the three tested plant pathogenic bacteria. Most noteworthy is the inhibitory rates of PA on Xanthomonas oryzae pv. oryzae ( Xoo ), X. oryzae pv. oryzicola ( Xoc ) and X. axonopodis pv. citri ( Xac ) of 93.6%, 92.1% and 86.1%, respectively, which are better than the control drug, bismerthiazol (63.4%, 61.2% and 53.7% at 100 μg mL −1 concentration). Furthermore, the EC 50 value of PA against Xoo , Xoc and Xac was 52.2, 60.0 and 65.1 μg mL −1 , respectively, superior to 72.9, 64.2 and 70.1 μg mL −1 of the control drug. Moreover, the anti- Xoo mechanistic studies revealed that PA exerted its antibacterial effects by increasing the permeability of the bacterial membrane, reducing the extracellular polysaccharide content and inducing morphological changes in bacterial cells. CONCLUSION A novel β -carboline alkaloid, PA , was prepared by biomimetic total synthesis. Its significant antibacterial activity was closely related to the permeation of bacterial cell membranes, which was confirmed by anti- Xoo mechanistic studies. More importantly, the structure could be regarded as a model for developing novel bactericides. © 2023 Society of Chemical Industry.
研究领域:
植物化学
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植物病理学
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有机合成
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）