Review
Chemistry, Multidisciplinary
Alexia N. Kim, Aurapat Ngamnithiporn, Emily Du, Brian M. Stoltz
Summary: This review discusses the general structure and biosynthesis of THIQ alkaloids and provides an overview of recent advancements in their total synthesis from 2002 to 2020. It highlights novel synthetic designs and modern chemical methodologies used in recent chemical syntheses.
Review
Biochemistry & Molecular Biology
Yi Gao, Ni Tu, Xiaoting Liu, Kangkang Lu, Siyu Chen, Ju Guo
Summary: This article summarizes a family of tetrahydroisoquinoline (THIQ) alkaloids among natural products, including Renieramycins, Ecteinasicdins, Tetrazaomine, and Lemonomycin. Most of these natural compounds have strong antitumor activities, and the family member ET-743 has been marketed for the treatment of advanced soft tissue tumors and ovarian cancer. Due to the excellent biological activity and complex chemical structure, these THIQ alkaloids have attracted great interest from biologists and chemists, with many synthetic chemists dedicating significant efforts to their total synthesis in the past decade. The recent advances in the total synthesis of these THIQ alkaloids are reviewed in this article.
CHEMISTRY & BIODIVERSITY
(2023)
Review
Chemistry, Multidisciplinary
Debobrata Paul, Ashis Kundu, Sanu Saha, Rajib Kumar Goswami
Summary: This feature article highlights total synthesis as a reliable tool for confirming the structure of natural products. Despite advances in spectroscopic techniques, structural misassignments of natural products remain common. Recent case studies have shown that chemical synthesis can be used to revise the structures of natural products.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Xikang Zheng, Yan Li, Mengtie Guan, Lingyue Wang, Shilong Wei, Yi-Cheng Li, Chin-Yuan Chang, Zhengren Xu
Summary: A unified strategy for the biomimetic total synthesis of the spiroindimicin family of natural products was reported. Key transformations include one-pot two-enzyme-catalyzed oxidative dimerization and regioselective bond formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Anas Ansari, Amol B. Gorde, Ramesh Ramapanicker
Summary: An enantioselective route has been developed for the synthesis of C-1 substituted tetrahydroisoquinoline natural products. Six different natural products were successfully synthesized from a single aldehyde using proline-catalyzed asymmetric alpha-hydrazination reaction. The highly enantioselective introduction of an amino group allowed for the synthesis of (-)-calycotomine, (-)-salsolidine, (-)-carnegine, (+)-homolaudanosine, (+)-homoprotoberberine and (thorn)-crispine A.
Review
Chemistry, Multidisciplinary
Huilin Li, Jing Zhang, Xuegong She
Summary: This MiniReview demonstrates the achievements in the construction of the diquinane ring system in the past decade, discussing the strategic synthesis of the diquinane unit and its impact on the field of natural product total synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Haoran Dong, Dachao Hu, Benke Hong, Jin Wang, Xiaoguang Lei
Summary: The first total syntheses of four natural antibiotics, vermisporin, PF1052/AB4015-A, AB4015-L, AB4015-B, and one hydrogenated natural product derivative, AB4015-A2, featuring a tetramic acid bearing cis-decalin ring, are reported. The functionalized cis-decalin ring was constructed via a diastereoselective intramolecular Diels-Alder (IMDA) reaction, with a rare endo-boat transition state. The efficient installation of the sterically hindered epoxy group in vermisporin, PF1052/AB4015-A, and AB4015-L was achieved through an intramolecular neighboring-group-oriented strategy, and the desired tetramic acid structure was obtained through a one-pot aminolysis/Dieckmann condensation cascade using L-amino acid derivatives. The total synthesis allowed for the unequivocal verification of the absolute configuration of these natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Tomoya Mashiko, Yuta Shingai, Jun Sakai, Shogo Kamo, Shinya Adachi, Akinobu Matsuzawa, Kazuyuki Sugita
Summary: In this study, the first total synthesis of cochlearol B, a meroterpenoid natural product with a unique pentacyclic structure, was described. Key steps including oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition allowed efficient access to cochlearol B with a longest linear sequence of 16 steps and 9% overall yield. Single-crystal X-ray crystallographic analysis confirmed the stereochemistry of cochlearol B.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Soumik De, Aritra Kumar Dan, Raghaba Sahu, Sagarika Parida, Debadutta Das
Summary: Gold catalysis is a popular and highly innovative field in catalysis research, providing new approaches for chemical transformations from simple starting materials. The application of gold catalysis in the total synthesis of natural products has successfully addressed complex challenges and achieved significant progress.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Review
Chemistry, Organic
Takaaki Sato, Takahiro Suto, Yoshiyuki Nagashima, Shori Mukai, Noritaka Chida
Summary: Skipped dienes, found in various biologically active natural products, have relatively undeveloped synthesis methods compared to conjugated dienes due to challenges posed by the sp(3)-hybridized carbon between two olefins. Recent advances in the synthesis of skipped dienes for total synthesis of complex natural products are classified into three categories, focusing on methods to achieve both high stereoselectivity and convergency.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Lukas Anton Wein, Klaus Wurst, Thomas Magauer
Summary: The study presented the construction of seven novel ent-trachylobane diterpenoids using a bioinspired synthetic strategy. Enantioselective and scalable access to five ent-trachylobanes was achieved in the first phase, with one compound produced on a 300 mg scale. Chemical C-H oxidation methods were then used in the second phase to selectively convert two higher functionalized ent-trachylobanes, revealing the potential and limitations of established protocols for complex molecule synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Han Chen, Zesheng Li, Peng Shao, Haosen Yuan, Si-Cong Chen, Tuoping Luo
Summary: A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described, which involves the Claisen rearrangement, transannular [2+2] photocycloaddition, ring-opening reaction, and subsequent late-stage alkylations and reduction to forge the characteristic skeleton.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Chemistry, Multidisciplinary
Suman Chakrabarty, Evan O. Romero, Joshua B. Pyser, Jessica A. Yazarians, Alison R. H. Narayan
Summary: The total synthesis of structurally complex natural products remains an exciting area of research, with recent advancements in biocatalysis allowing for the application of enzymes in constructing complex molecules. The utilization of enzymes alongside small molecule-based approaches has enabled concise chemoenzymatic routes to natural products, demonstrating the potential for selective oxidation reactions and late-stage diversification of complex scaffolds.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Kevin Rafael Sokol, Thomas Magauer
Summary: This review provides an overview of synthetic methods and strategies for constructing oxepin and dihydrooxepin motifs in the context of natural product synthesis, highlighting key steps of each example.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Medicinal
Min Woo Ha, Jonghoon Kim, Seung-Mann Paek
Summary: The discovery of novel marine natural products often leads to efforts in finding new therapeutic ingredients. Due to the complexity and uniqueness of substances produced in the marine environment, there have been cases where the structures were incorrectly assigned despite the use of modern chemical techniques. Organic chemical synthesis and thorough spectroscopic data inspection are crucial in refuting inaccuracies in proposed structures.
Review
Biochemistry & Molecular Biology
Sanghee Lee, Jonghoon Kim, Minseob Koh
Summary: This review discusses the advances in the genetic code expansion-based strategies to site-specifically introduce fluorophores at a defined position of proteins and their applications in bio-imaging.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Young-Hee Shin, Kiyoung Jeong, Jihye Lee, Hyo Jung Lee, Junhyeong Yim, Jonghoon Kim, Seungtaek Kim, Seung Bum Park
Summary: A novel small molecule has been discovered that can inhibit SARS-CoV-2 infection by modulating ACE2 without impairing its normal function. This finding may provide a new therapeutic strategy to block viral entry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Youngjun Lee, Dahham Kim, Seung Bum Park
Summary: The photophysical behaviors of fluorescent molecules largely determine their utility in biological studies. This study proposes a novel heterocyclic core fluorescent platform that allows flexible control of its photophysical properties through synergistic interaction between functional groups. The platform enables broad tunability of emission wavelength, Stokes shift, fluorescent brightness, and charge transfer characteristics. Furthermore, by reorganizing functional groups, the platform can be used to develop live-cell imaging probes with distinct optical features.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Wan Gi Byun, Donghyun Lim, Seung Bum Park
Summary: This review discusses the potential of targeting PRIs using small molecules, the tools for observing PRIs in biochemical and cell-based experiments, and various PRI modulators. Emerging technologies and challenges in the development of PRI modulators are also highlighted.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Yun Lim Jung, Sourav Sarkar, Jaeyoung Ha, Seung Bum Park, Kyo Han Ahn
Summary: In this study, a new TRC platform was developed for fluorescent molecule labeling on biomolecules under spatiotemporal control. The o-quinone methide chemistry was utilized to achieve efficient labeling of proteins using different aryl alcohol fluorophores. The versatility and uniqueness of this TRC system were demonstrated in both cellular and tissue bioconjugation, showing potential for in situ fluorophore labeling of proteins in biological systems.
BIOCONJUGATE CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Jongdoo Choi, Jiyeun Ahn, Jieun Bae, Minseob Koh
Summary: The expression of genes of interest can be controlled by providing external stimuli such as temperature shifts and light irradiation, which trigger structural changes in stimuli-sensitive biomolecules within the cell. Over the past two decades, various groups have reported genetic circuits that manipulate gene expression using natural or engineered stimuli-sensitive modules.
Review
Chemistry, Medicinal
Jesang Lee, Seung Bum Park
Summary: Covalent inhibitors have been accepted as a practical tool for targeting previously undruggable proteins. Despite the clinical success, there are still unmet medical needs. Categorizing and reviewing covalent inhibitors provide insights into the future development of this field.
Article
Chemistry, Medicinal
Hyun-Jin Jang, Yae Jin Yoon, Jiyeon Choi, Yu-Jin Lee, Sangku Lee, Wansang Cho, Wan Gi Byun, Seung Bum Park, Dong Cho Han, Byoung-Mog Kwon
Summary: Metastasis is a major cause of cancer death and treatment failure. Previous research identified benproperine (Benp) as a potential inhibitor of cancer cell migration. However, the active stereoisomer of Benp was unclear. This study found that S-Benp is the active stereoisomer, which effectively inhibits cancer cell migration and invasion without affecting normal cells. The study also validated the binding of S-Benp to ARPC2, suggesting its potential as a metastasis inhibitor.
Article
Chemistry, Multidisciplinary
Wansang Cho, Solchan Won, Yoona Choi, Sihyeong Yi, Jong Beom Park, Jun-Gyu Park, Caroline E. Kim, Chintam Narayana, Ju Hee Kim, Junhyeong Yim, Young Il Choi, Dong-Sup Lee, Seung Bum Park
Summary: Modulating target proteins via the ubiquitin-proteasome system has expanded the scope of pharmacological inventions. STING, an auspicious target for immunotherapy, has been found to have importance as well as utility in immunotherapy outcomes. The proposed UPPRIS strategy utilizing the small molecule SB24011 enhances STING immunity and potentiates the efficacy of immunotherapy, suggesting targeted protein upregulation as a promising approach for immuno-oncology.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Kannan Vaithegi, Sihyeong Yi, Ji Hyae Lee, Begur Vasanthkumar Varun, Seung Bum Park
Summary: Substituted pyridines with diverse functional groups are important in bioactive molecules. This study reports a method for introducing multiple functional groups to pyridine via ring cleavage reaction. The robustness of the methodology was demonstrated by synthesizing a variety of 5-aminoaryl and 5-phenol pyridines, and the application of the methodology provided a privileged pyridine scaffold for drug conjugation.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biology
Jinjoo Jung, Jongbeom Park, Mingi Kim, Jaeyoung Ha, Hana Cho, Seung Bum Park
Summary: The small molecule SB2301 activates lipophagy and alters lipid droplet membrane composition, with the ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) being a potential target of the compound. The excessive accumulation of lipid droplets is associated with various diseases, and understanding the molecular mechanism of LD degradation is important for academic and industrial research. Lipophagy, a selective autophagy process, has gained attention in the research community. This study reveals a novel lipophagy mechanism through the use of SB2301, which activates ubiquitin-mediated lipophagy. The potential target protein PCYT2 is identified, and SB2301 induces PCYT2 translocation to the LD surface and alters the LD membrane composition, leading to the activation of the lipophagy process.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Dahham Kim, Hayoung Son, Seung Bum Park
Summary: This study synthesized a series of BODIPY-Tz probes for bioorthogonal cellular imaging and discovered their unique fluorescence behavior on BCN and TCO. Additionally, dual-color bioorthogonal cellular imaging with a single probe was achieved for the first time.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Medicine, Research & Experimental
Soo Yeon Baek, Jeehee Lee, Taegwan Kim, Hyelim Lee, Hoon-Seong Choi, Hahnbeom Park, Minseob Koh, Eunha Kim, Michael E. Jung, Dimitrios Iliopoulos, Jeong-Yeon Lee, Jonghoon Kim, Sanghee Lee
Summary: In this study, a novel HDAC inhibitor, 5, was developed and shown to suppress microglial activation and alleviate depression-like behavior by inducing autophagy and inhibiting nitric oxide production. These findings suggest HDAC11 as a potential therapeutic target for depressive disorder.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Editorial Material
Chemistry, Medicinal
Wansang Cho, Jung Ho Lee, Seung Bum Park
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hana Cho, Bo Young Choi, Young-Hee Shin, Sang Won Suh, Seung Bum Park
Summary: In this study, we investigated the neuroprotective function of SB1617 against tau aggregation mediated by microglia. Our findings showed that SB1617 deactivated pathogenic M1-like microglia, reduced the secretion of pro-inflammatory cytokines, induced microglial polarization towards the M2 phenotype, and enhanced phagocytic function. In addition, we observed the clearance of extracellular pathogenic tau aggregates through LC3-associated phagocytosis. Furthermore, in vivo experiments confirmed the neuroprotective effects of SB1617 in a mouse model of traumatic brain injury by reducing pathogenic tau levels through microglia-mediated anti-inflammatory activity. Our results indicate that SB1617-mediated microglial surveillance with LC3-associated phagocytosis is a critical molecular mechanism in the regulation of tau proteostasis.
ACS CHEMICAL NEUROSCIENCE
(2023)