Article
Chemistry, Multidisciplinary
Haiting Yin, Qin Ma, Yushan Wang, Xiaoxia Gu, Zhijun Feng, Yunjun Wu, Ming Wang, Shaoyin Wang
Summary: The study presents a facile and efficient route to tetrahydro-beta-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative annulation reactions. The reaction involves a cascade sequence of Friedel-Crafts-type alkylation followed by intramolecular Click reaction, forming multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.
Article
Chemistry, Applied
Jie Xu, Cheol K. Chung, Andrew McClory, Kyle A. Mack, Michael E. Dalziel, Alec Fettes, Kyle Clagg, Ngiap-Kie Lim, Georg Wuitschik, Christian Jenny, Laure Finet, Michael Kammerer, Haiming Zhang, Remy Angelaud, Francis Gosselin
Summary: GDC-9545, a selective estrogen receptor degrader, is being developed as a treatment for ER+/HER2- breast cancer. A robust and efficient manufacturing process has been developed to produce GDC-9545.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Organic
Gourishetty Srikanth, Anil Ravi, Anusha Sebastian, Jobi Joseph, Monther A. Khanfar, Mohammed I. El-Gamal, Raed A. Al-Qawasmeh, Ihsan A. Shehadi, Scott McN. Sieburth, Imad A. Abu-Yousef, Amin F. Majdalawieh, Taleb H. Al-Tel
Summary: A new class of pseudo-NP collection was developed by connecting tryptamines with a furanose derivative and subjecting the product to a ring distortion strategy. This led to diastereoselective synthesis of camptothecin-like compounds through a cascade of Pictet-Spengler reaction, Michael addition reaction, oxidative-ring enlargement, and transannular aldol cyclization. The obtained diastereoselectivity was verified using density functional theory (DFT) calculations.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Qi-Wen Shen, Wei Wen, Qi-Xiang Guo
Summary: The first catalytic asymmetric cascade Heck-alkylation reaction of NH2-unprotected amino acid esters with N-(2-iodophenyl)allenamides is reported in this work. The reaction proceeds smoothly using a combining catalytic system comprising a chiral aldehyde, a chiral palladium complex, and the Lewis acid ZnCl2, giving optically active alpha-alkyl tryptophan derivatives in moderate to good yields and excellent enantioselectivities. The target products can be converted into other structurally complex chiral indoles without the loss of enantioselectivities.
Article
Chemistry, Multidisciplinary
Remi Andres, Qian Wang, Jieping Zhu
Summary: A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been achieved by several key steps, including a catalyst-controlled asymmetric Pictet-Spengler reaction, oxidative cleavage, and intramolecular nucleophilic addition. The synthesis confirmed the absolute configuration of these natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Integrative & Complementary Medicine
Chen Bo-Ru, Gao Cheng-Long, Liu Jin, Guo Yue-Wei, Jiang Jian-Lan, Pang Tao, Li Xu-Wen
Summary: Diversity-oriented synthesis was used to design and synthesize a series of indole-containing marine natural product derivatives for evaluation of their anti-inflammatory activity. One of the newly synthesized derivatives showed promising activity by inhibiting cytokine release, suggesting the potential of marine indole alkaloids as leads for anti-inflammatory drug discovery.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Chemistry, Organic
Bilal O. Alkubaisi, Anil Ravi, Gourishetty Srikanth, Anusha Sebastian, Monther A. Khanfar, Mohammed I. El-Gamal, Scott McN. Sieburth, Afnan I. Shahin, Taleb H. Al-Tel
Summary: The development of robust and step-economic strategies to access structurally diverse drug-like compound collections, specifically quinazolinone ring system, is still a challenge. To address this, a metal-free operation using Friedel-Crafts and aza-Michael addition reactions is reported, enabling rapid access to C6-substituted pyrroloquinazolinone and pyrroloquinazolinone architectures. This operationally simple protocol is compatible with a wide range of starting materials and offers a promising approach for the design of compound libraries for drug design and discovery programs.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Jianxiong Zhao, Daniel Mendez-Sanchez, Rebecca Roddan, John M. Ward, Helen C. Hailes
Summary: The study demonstrates the use of wild-type NCS and selected variants with various ketones to access challenging non-natural THIAs. Some NCS variants were found to accept fused bicyclic ketones and diketones, providing new insights into the rational for this acceptance through in silico modeling.
Article
Chemistry, Organic
Ahreum Kim, Junsoo Moon, Chanhee Lee, Jayoung Song, Jongchan Kim, Yongseok Kwon
Summary: In this study, a highly enantioselective Pictet-Spengler reaction for the synthesis of axially chiral tetrahydroisoquinolines via dynamic kinetic resolution is reported. The cyclization catalyzed by chiral phosphoric acids leads to the formation of single regioisomeric isoquinolines with excellent enantioselectivities up to 99% ee around the C-C bond. The effectiveness of this protocol is demonstrated for a wide range of substrates, with enantiodivergence observed depending on the substituents on the catalysts.
Article
Chemistry, Multidisciplinary
Annina Burhop, Sukdev Bag, Michael Grigalunas, Sophie Woitalla, Pia Bodenbinder, Lukas Brieger, Carsten Strohmann, Axel Pahl, Sonja Sievers, Herbert Waldmann
Summary: By combining fragments derived from natural products in new ways, a collection of pseudo-NPs known as indofulvins has been created. These compounds define a new chemotype of autophagy inhibitors targeting mitochondrial respiration, showing potential pharmacological properties.
Article
Chemistry, Organic
Long Dan, Zhiqiang Liu, Liang Huo, Hesi Yang, Jiuzhou Yi, Xingang Xie, Xuegong She
Summary: A concise total synthesis of (+)-tabertinggine was achieved in 12 steps with an overall yield of 6.1% through a Pictet-Spengler condensation/lactamization cascade reaction.
Article
Chemistry, Applied
Liu-Yang Pu, Fan Yang, Ji-Qiang Chen, Ying Xiong, Jian-Hua Xie, Qi-Lin Zhou
Summary: The enantioselective total synthesis of the pentacyclic proaporphine alkaloid (-)-misramine was achieved, featuring key reactions including Pictet-Spengler cyclization and Baeyer-Villiger oxidation. The absolute configuration of the pentacyclic framework was determined through X-ray single-crystal analyses.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Michael E. Pyne, Vincent J. J. Martin
Summary: This review outlines the increasing activity surrounding the production of natural, semisynthetic, and new-to-nature THIQ metabolites in engineered microbial systems, which has accelerated THIQ pathway discovery and engineering, and spurred the development of highly productive microbial strains.
CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Corin C. Wagen, Spencer E. McMinn, Eugene E. Kwan, Eric N. Jacobsen
Summary: Research in the field of asymmetric catalysis has made significant progress, enabling the efficient synthesis of chiral building blocks, pharmaceuticals, and natural products. Traditional discovery campaigns only focus on a single model substrate, limiting the selection for both enantioselectivity and substrate generality. This study proposes a practical approach using multiple model substrates for high-throughput chiral analysis, allowing for simultaneous selection of both enantioselectivity and generality in asymmetric catalytic reactions from the beginning.
Article
Chemistry, Multidisciplinary
Remi Andres, Fenggang Sun, Qian Wang, Jieping Zhu
Summary: An asymmetric Pictet-Spengler reaction of alpha-ketoesters was developed, achieving high yields and ee values. The reaction mechanism was proposed to involve deprotonation of the pentahydro-beta-carbolinium ion as the rate- and enantioselectivity-determining step. This methodology was successfully applied in the enantioselective total synthesis of (+)-alstratine A, and the remeasurement of its [a](D) value revealed a correction in the initial report.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Youjuan Zhu, Shiyang Li, Yichao Kong, Huimin Zhao, Yuanzhuo Hu, Jingyi Meng, Xiabin Chen, Shurong Hou, Xiachang Wang
Summary: Two new terragine analogs, with special succinimide and aminopentane moieties, were isolated from the fermentation broth of Bacillus sp. SH-1.2-ROOT-18, an endophyte previously discovered from the root of Dendrobium officinale. The structures were determined through comprehensive 1D/2D NMR and MS data analysis, along with complete NMR assignments for the first reported naturally occurring metabolite 3.
NATURAL PRODUCT RESEARCH
(2022)
Article
Biochemical Research Methods
Shiyang Li, Lu Chen, Yanhui Li, Tao Hu, Xiaoyan Zhang, Lihong Chen, Xiachang Wang
Summary: The study established a UPLC fingerprint method for quality evaluation of Rheum palmatum and comparison with other related species. The results showed that the fingerprint profiles could distinguish Rheum palmatum from different original plants and confusable varieties. Principal component analysis indicated discrepancies in chemical components among three different species of rhubarb.
JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
(2021)
Article
Chemistry, Multidisciplinary
Yujian Mao, Jing Jiang, Dandan Yuan, Xiuzhen Chen, Yanan Wang, Lihong Hu, Yinan Zhang
Summary: Methyl groups are commonly found in bioactive molecules, and site-specific methylation has become an important strategy for their structural functionalization. In this study, a highly regioselective peri- and ortho-C-H methylation of 1-naphthaldehyde was achieved using a transient ligand strategy, leading to the synthesis of various methyl-substituted naphthalene frameworks. The mechanism of peri-methylation and ortho-methylation was investigated, providing insights into the control factors and energetically favorable pathways.
Article
Biochemical Research Methods
Abigael J. Kosgei, Mitchell D. Miller, Minakshi Bhardwaj, Weijun Xu, Jon S. Thorson, Steven G. Van Lanen, George N. Phillips
Summary: This paper reports the crystal structure of DynF, a gene product within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight-stranded beta-barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten-membered ring of the enediyne core.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2022)
Article
Plant Sciences
Qian He, Simin Li, Yue Fan, Yu Liu, Yu Su, Zhen Zhou, Yi-Nan Zhang, Guo-Li Li, Li Rao, Chuan-Rui Zhang
Summary: Nine new complex flavanones, named cryptometcones A-I (1-9), along with four known analogues, were isolated from Cryptocarya metcalfiana. Their structures and absolute configurations were determined through spectroscopic data analysis and ECD calculations. Compounds 3-5, 8, and 9 exhibited cytotoxicity against the HCT-116 cancer cell line.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Environmental Sciences
James C. Hower, Zeljka Fiket, Kevin R. Henke, John K. Hiett, Jon S. Thorson, Madan Kharel, Shifeng Dai, Luis F. O. Silva, Marcos L. S. Oliveira
Summary: The mineralogical and geochemical features of mining and processing wastes collected from Owen County, part of the Central Kentucky Lead-Zinc district, were investigated. The main minerals found in the samples were calcite, quartz, and dolomite, with sphalerite, galena, and barite as the principal sulfides and sulfates. The geochemistry of major elements reflected the mineralogy, while trace elements showed different groupings between minerals. The data illustrated the processes and conditions that control sulfide-mineral oxidation and its potential environmental impact.
JOURNAL OF SOILS AND SEDIMENTS
(2022)
Article
Chemistry, Organic
Yujian Mao, Zhen Xia, Lihong Hu, Yinan Zhang
Summary: In this study, new methods for synthesizing methylated naphthalene natural products were disclosed using simple and commercially available naphthalene molecules. These methods overcome the challenges of low content in plants and lack of synthetic methods.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemical Research Methods
Rongbin Wang, Jennifer Nguyen, Jacob Hecht, Nora Schwartz, Katelyn Brown, Larissa Ponomareva, Magdalena Niemczura, Dino van Dissel, Gilles P. van Wezel, Jon S. Thorson, Mikko Metsa-Ketela, Khaled A. Shaaban, S. Eric Nybo
Summary: By developing the BIOPOLYMER toolbox, we have overcome the limitations of slow growth and lack of genetic tools in actinomycetes for the synthesis of anthracyclinones. We successfully improved the production host and optimized the production of anthracyclinones, identifying optimal combinations for different molecules. Additionally, we demonstrated the moderate cytotoxicity of the anthracyclinones against multiple cancer cell lines.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Chemistry, Medicinal
Ping Wang, Hongqiong Yang, Weijiang Lin, Jingxian Zhou, Chengli Yu, Yinan Zhang, Yi Liu, Lingyu Ma, Mengting Li, Yang Hu, Qi Lv, Jian Liu, Lihong Hu
Summary: The D5 compound has been found to inhibit the differentiation of Th17 cells by suppressing PKM2-mediated glycolysis, restoring the Th17/Treg balance, and showing promising therapeutic effects against ulcerative colitis, making it a potential novel anti-UC candidate.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Applied
Junyang Wang, Han Li, Yanhui Li, Aiping Yang, Sheng Bao, Yuntian Zhang, Qing Du, Zongping Zheng, Xiachang Wang
Summary: Two new prenylated flavonoids named sinoflavonoids NJ and NK (1-2), along with ten known compounds, were isolated from the fruits of Podophyllum hexandrum Royle. The chemical structures were determined through NMR spectroscopic data and MS analysis. Sinoflavonoid NJ (1) with an unusual 5,11-dioxabenzo[b]fluoren-10-one skeleton was firstly reported from Berberidaceae. The isolated flavonoids were tested for their anti-inflammatory activity using the LPS-induced RAW 264.7 mouse macrophages model. Sinoflavonoid NJ (1) showed the most potent inhibition on nitric oxide production with an IC50 value of 0.06 μM.
NATURAL PRODUCT RESEARCH
(2023)
Article
Plant Sciences
Jucelia Iantas, Daiani Cristina Savi, Larissa V. Ponomareva, Jon S. Thorson, Juergen Rohr, Chirlei Glienke, Khaled A. Shaaban
Summary: Chemical investigation of the endophyte Pseudofusicoccum stromaticum CMRP4328 isolated from the medicinal plant Stryphnodendron adstringens resulted in the discovery of ten compounds, including two new dihydrochromones. The study found that four of these compounds exhibited antifungal activity against the citrus pathogen Phyllosticta citricarpa, and the development of citrus black spot symptoms in citrus fruits was also inhibited by two of the compounds. These findings suggest that further research on the strain CMRP4328 of P. stromaticum and its metabolites is warranted for the control of citrus black spot disease.
Article
Biochemistry & Molecular Biology
Han Li, Hanghang Wang, Aiping Yang, Mingzhen Xue, Junyang Wang, Qi Lv, Jian Liu, Lihong Hu, Yinan Zhang, Xiachang Wang
Summary: Researchers found that active saponin constituents from Gynostemma pentaphyllum can protect the liver. They specifically studied a gypenoside, XLVI, and found that it can ameliorate both acute and chronic liver injuries and reduce fibrogenesis. XLVI inhibited the activation of hepatic stellate cells and ECM deposition in vitro. The study also showed that XLVI upregulated the protein expression of protein phosphatase 2C alpha, enhancing its activity along with a PP2C alpha agonist, gypenoside NPLC0393. These findings shed light on the molecular mechanisms and potential therapeutic function of Gynostemma pentaphyllum in treating liver fibrosis.
Article
Biochemistry & Molecular Biology
Aiping Yang, Yu Hong, Fengjuan Zhou, Ling Zhang, Youjuan Zhu, Chang Wang, Yang Hu, Li Yu, Lihong Chen, Xiachang Wang
Summary: One of the biggest concerns in global health today is antibiotic resistance, highlighting the need to find alternative solutions. This study focuses on investigating endophytic microorganisms from medicinal plants in Fenghuang Mountain in order to discover new antibiotics. The research demonstrates the potential of these microbes to produce a variety of natural products, making them an important source for new antibiotics.
Correction
Multidisciplinary Sciences
Minakshi Bhardwaj, Zheng Cui, Erome Daniel Hankore, Faruk H. Moonschi, Hoda Saghaeiannejad Esfahani, Edward Kalkreuter, Chun Gui, Dong Yang, George N. Phillips, Jon S. Thorson, Ben Shen, Steven G. Van Lanen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Organic
Jing Jiang, Yujian Mao, Yaoyu Lin, Jiayi Shen, Yinan Zhang
Summary: This article presents a total synthesis of hemigossypol through ligand-directed C-H oxygenations and completing the synthesis in 10 steps with a total yield of 9.5%. By adjusting the order of hydroxyl and isopropyl group installation, our strategy based on direct functionalization of a naphthalene ring shortens the route and improves efficiency compared to conventional approaches. This regiospecific approach holds promise for rapid access to diverse derivatives of gossypol for biological studies.
ORGANIC CHEMISTRY FRONTIERS
(2023)
