Article
Chemistry, Organic
Shoma Ariyoshi, Kazuhiko Sakaguchi, Takahiro Nishimura
Summary: The reaction proceeded via tandem Hosomi-Sakurai/Prins cyclization to produce polysubstituted tetrahydropyranones with high stereoselectivity. It is compatible with various aldehydes and ketones, and the optical purity of the starting material was well-retained in the final products.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Daichi Mizukami, Kei Iio, Mami Oda, Yu Onodera, Haruhiko Fuwa
Summary: Tetrahydropyran-containing macrolactones were synthesized using gold and ruthenium catalysis through a three-step reaction sequence, demonstrating high synthetic efficiency and good diastereoselectivity. The synthesis of an anticancer marine macrolide showcased the potential application of this reaction sequence in the synthesis of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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, Organic
Youssef Nassar, Fabienne Fache, Beatrice Pelotier, Olivier Piva
Summary: A Prins reaction followed by intramolecular Friedel-Crafts reaction was used to synthesize novel [4.4.3]propellane structures from readily available cyclic homoallylic alcohols.
SYNTHESIS-STUTTGART
(2022)
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
Yunpeng Ji, Benke Hong, Ivan Franzoni, Mengyang Wang, Weiqiang Guan, Hongli Jia, Houhua Li
Summary: In this paper, a 9-step enantioselective total synthesis of (+)-hyperforin and (+)-pyrohyperforin was described, starting from commercially available allylacetone. The synthesis involved important reactions such as the enantioselective deconjugative alpha-alkylation using chiral lithium amides as stereodirecting auxiliaries, the HfCl4-mediated carbonyl alpha-tert-alkylation to form the intricate bicyclo[3.3.1]nonane framework, an abiotic cascade pyran formation, and a selective 1,4-semihydrogenation of polyenes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Lisa-Catherine Rosenbaum, Maximilian Haefner, Tanja Gaich
Summary: A racemic and scalable enantioselective total synthesis of (+)-waihoensene was achieved, featuring an angular triquinane substructure with an all-cis-fused tetracyclic backbone and six contiguous stereocenters, four of which are quaternary. Enantioselectivity was introduced at an early stage, and key structural features were efficiently installed through several diastereoselective reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Zhen Yang
Summary: The total synthesis endeavors contribute to the discovery and invention of new synthetic reactions to advance organic synthesis. Bioactive compounds share common features, such as molecular complexity, protein-binding ability, structural rigidity, and three-dimensionality. Total synthesis offers an alternative solution for generating scarce natural products and their derivatives for studying their biological functions.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Keith P. Reber, Emma L. Niner
Summary: The synthesis of amino acids (-)-halichonic acid and (-)-halichonic acid B has been successfully achieved in ten steps starting from commercially available (-)-alpha-bisabolol. A new purification method involving recrystallization of the benzamide derivative of (-)-7-amino-7,8-dihydrobisabolene has been developed to obtain enantiomerically pure form. The key intramolecular aza-Prins reaction formed the characteristic ring system of halichonic acid and halichonic acid B in a specific ratio.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Wai Fung Cheng, Shiqiang Ma, Yin Tung Lai, Yuen Tsz Cheung, Kornkamon Akkarasereenon, Yiqin Zhou, Rongbiao Tong
Summary: An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed using bismuth tribromide as both an efficient Lewis acid and a bromide nucleophile source. This approach enables the construction of highly functionalized 9-azabicyclo[3.3.1]nonanes, which are valuable building blocks for alkaloid natural products and drug molecules. The application of this method to the total synthesis of six indole alkaloids demonstrates its significant synthetic utility.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Nabakumar Bera, Shantanu Samanta, Debayan Sarkar
Summary: The manuscript describes a ruthenium-catalyzed atom-economic coupling method for the synthesis of beta-hydroxyenones, which can further lead to the high-yield and high diastereoselective synthesis of tetrahydro-4H-pyran-4-ones. Through intramolecular aldol condensation and palladium-catalyzed oxidative aromatization, hexahydro-6H-isochromen-6-ones and isochromanols can be synthesized from highly substituted tetrahydro-4H-pyran-4-ones with excellent yield and diastereoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Sudip Shit, Surjya Kumar Bora, Archana Kumari Sahu, Anil K. Saikia
Summary: This study demonstrates the synthesis of spiro[furan-2,1'-isoindolin]-3'-ones from 2-(4-hydroxybut-1-yn-1-yl)benzonitriles and aryl aldehydes. The reaction involves the formation of dihydrofuranylideneisoindolinone through intramolecular Prins and Ritter reactions, followed by ring opening and cyclization to produce the spiro-cyclic compounds.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
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)
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
Hong-Gang Cheng, Zhenjie Yang, Ruiming Chen, Liming Cao, Wen-Yan Tong, Qiang Wei, Qingqing Wang, Chenggui Wu, Shuanglin Qu, Qianghui Zhou
Summary: A concise total synthesis of (-)-berkelic acid is reported in eight linear steps, featuring a Catellani reaction/oxa-Michael cascade, a one-pot deprotection/spiroacetalization operation, and a late-stage Ni-catalyzed reductive coupling. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process, supported by DFT calculations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Anna Bay, Keegan P. Fitzpatrick, Gisela A. Gonzalez-Montiel, Abdikani Omar Farah, Paul Ha-Yeon Cheong, Karl A. Scheidt
Summary: This study reports the light-driven synthesis of aliphatic and alpha-amino ketones using single-electron NHC operators. Computational and experimental results show that the reactivity of the key radical intermediate depends on the substrate and can be modulated through steric and electronic parameters of the NHC. This methodology is showcased in the direct late-stage functionalization of amino acids and pharmaceutical compounds, highlighting the utility of single-electron NHC operators.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Joshua L. Zhu, Karl A. Scheidt
Summary: Despite recent advancements in the selective generation and coupling of organic radical species, the alkoxycarbonyl radical remains underexplored relative to other carbon-containing radical species. Inspired by strategies using dual N-heterocyclic carbene catalysis and photocatalysis, dimethylimidazolium esters were prepared as alkoxycarbonyl radical surrogates under photocatalytic conditions, showing synthetic utility in coupling with an oxidatively generated alkyl radical to form esters.
Article
Chemistry, Medicinal
Ada J. Kwong, Thao N. D. Pham, Hannah E. Oelschlager, Hidayatullah G. Munshi, Karl A. Scheidt
Summary: The study presents two potent MEK4 inhibitors which showed significant reduction in phospho-JNK and antiproliferative properties against pancreatic cancer cell lines. Additionally, molecular inhibition of the MEK4 pathway activates the MEK1/2 pathway, with the combination of MEK1/2 and MEK4 inhibitors demonstrating synergistic effects against pancreatic cancer cells. These inhibitors provide insight into the crosstalk between MAPK pathways and new tools for elucidating the roles of MEK4 in disease states.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Applied
Pengzhi Wang, Keegan P. Fitzpatrick, Karl A. Scheidt
Summary: The research presents a method for synthesizing gamma-aryloxyketones via combined NHC/photoredox catalysis, where an α-aryloxymethyl radical is coupled with styrene derivatives and then with an azolium radical to produce the desired products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Review
Chemistry, Organic
Eric R. Miller, Karl A. Scheidt
Summary: This article summarizes the research on the total synthesis of bioactive alkaloids, highlighting the importance and achievements of catalytic asymmetric methods in this field, and providing new inspiration for future synthesis of these important natural products.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Anna Bay, Emelia J. Farnam, Karl A. Scheidt
Summary: This study presents a novel tandem carbene and photoredox-catalyzed process for the synthesis of substituted cycloalkanones, offering a new approach for constructing important cyclic scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Meghan J. Orr, Andrew B. Cao, Charles Tiancheng Wang, Arsen Gaisin, Adam Csakai, Alec P. Friswold, Herbert Y. Meltzer, John D. McCorvy, Karl A. Scheidt
Summary: This study identified a potential agonist activity of substituted tetrahydro-beta-carbolines across the 5-HT2 receptor family, laying a foundation for future research in neurological and psychiatric disorders.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Seunghwan Byun, Abdikani Omar Farah, Henry R. Wise, Andrew Katchmar, Paul H. -Y. Cheong, Karl A. Scheidt
Summary: This study reveals an approach for the copper-catalyzed synthesis of enantioenriched amides bearing an alpha-stereogenic center. The addition of an allyl copper species to an isocyanate allows access to alpha-substituted chiral amides in high yields and high-to-excellent enantioselectivities. The utility of alpha-vinyl beta-boryl amides in synthesis is highlighted by the diversification of products to afford highly useful scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Joshua L. Zhu, Cullen R. Schull, Anthony T. Tam, Angel Renteria-Gomez, Achyut Ranjan Gogoi, Osvaldo Gutierrez, Karl A. . Scheidt
Summary: Stable acyl azolium salts can undergo intermolecular HAT reaction upon LED irradiation to afford ketones.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Dalton R. Kim, Meghan J. Orr, Ada J. Kwong, Kristine K. Deibler, Hasan H. Munshi, Cory Seth Bridges, Taylor Jie Chen, Xiaoyu Zhang, H. Daniel Lacorazza, Karl A. Scheidt
Summary: The mitogen-activated protein kinase (MAPK) signaling cascade is essential for regulating various cellular activities across eukaryotes. In this study, a novel class of irreversible MAP2K7 inhibitors was designed and synthesized, with promising in vitro potency and selectivity, as well as favorable cellular activity. These compounds show potential as powerful tools for studying pediatric T cell acute lymphoblastic leukemia (T-ALL).
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Qiupeng Peng, Achyut Ranjan Gogoi, Osvaldo Gutierrez, Angel Renteria-Gomez, Karl A. Scheidt
Summary: This article reports a divergent process for the synthesis of α-hydroxy/amino ketones or β-keto-phosphonates through a light-induced coupling of activated carboxylic acids and alcohols/amines via single-electron chemistry. This process enables new carbon-carbon bond formation using a phosphorous linchpin strategy.
Article
Chemistry, Multidisciplinary
Seunghwan Byun, Meemie U. Hwang, Henry R. Wise, Anna V. Bay, Paul H. -Y. Cheong, Karl A. Scheidt
Summary: This study explores the enantioselective carbene-catalyzed radical-radical coupling reaction of acyl imidazoles and racemic Hantzsch esters, leading to the synthesis of chiral alpha-aryl aliphatic ketones. The method shows potential application in pharmaceutical synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Michael J. Rourke, Matthew J. McGill, Daniel Yang, Emelia J. Farnam, Joshua L. Zhu, Karl A. Scheidt
Summary: Potassium trifluoroborates have been widely used as coupling partners in organic synthesis, and also as radical precursors to generate carbon-centered radicals under oxidative conditions. These versatile reagents have found new applications in photoredox catalysis, including radical substitution, conjugate-addition reactions, and transition-metal dual catalysis. In addition, this photomediated redox-neutral process enables radical-radical coupling with persistent radicals in the absence of metals, which remains to be fully explored.
Article
Chemistry, Multidisciplinary
Jing Cao, Joshua L. Zhu, Karl A. Scheidt
Summary: In this study, a cerium-catalyzed acylation reaction was reported, which can acylate unactivated C(sp3)-H bonds under mild and operationally-friendly conditions. The reaction shows excellent generality, accommodating a wide range of feedstock chemicals, and facilitating the late-stage functionalization of pharmaceuticals.
Review
Chemistry, Multidisciplinary
Anna Bay, Karl A. Scheidt
Summary: Chemists have used the polarity reversal reactivity of N-heterocyclic carbenes (NHCs) to build key chemical bonds, and their redox properties enable the synthesis of stable radical species. This has greatly contributed to the field of synthetic chemistry and the revival of radical chemistry.
TRENDS IN CHEMISTRY
(2022)
