Review
Chemistry, Multidisciplinary
Krishnaji Tadiparthi
Summary: This review discusses the synthetic approaches of chiral and racemic forms of centrolobines from 2002 to date, highlighting the importance of construction of tetrahydropyran unit and generation of chirality in the synthesis process. It systematically presents various methods developed by different research groups in the total syntheses of centrolobines.
Article
Chemistry, Multidisciplinary
Wenqiang Zhou, Tao Zhou, Mengxing Tian, Yan Jiang, Jiaojiao Yang, Shuai Lei, Qi Wang, Chongzhou Zhang, Hanyue Qiu, Ling He, Zhen Wang, Jun Deng, Min Zhang
Summary: Through the development of a new method and key reactions, the concise, collective, and asymmetric total syntheses of four schizozygane alkaloids, including the first asymmetric synthesis, have been achieved in only 11-12 steps from tryptamines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Haruka Fujino, Masanori Nagatomo, Masayuki Inoue
Summary: Hikizimycin is a potent anthelmintic and antibacterial natural product with a complex structure that has attracted synthetic chemists since its structural determination in the early 1970s. Efforts have culminated in synthetic approaches including the synthesis of protected hikosamines and total synthesis of Hikizimycin, showcasing the evolution of modern natural product synthesis.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Feifei He, Shangbiao Feng, Yulong Zhao, Hongliang Shi, Xiaoguang Duan, Huilin Li, Xingang Xie, Xuegong She
Summary: A gold-catalyzed reaction is developed to access tricyclic cores using the commonly shared bicyclic decahydroquinoline motif. These cores are then used for the divergent total syntheses of five Lycopodium alkaloids in a concise manner. Key transformations include ring cyclization, hydration, fragmentation, and construction of specific motifs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Kaixiang Xu, Shan Mu, Huijuanzi Rao, Jialei Hu, Hanfeng Ding
Summary: The asymmetric total syntheses of (+)-vulgarisins A-E, which share a rare and highly oxygenated [5-6-4-5] tetracyclic core structure that were isolated from P. vulgaris Linn., have been described for the first time in a divergent manner. Key transformations include: 1) a catalytic asymmetric intramolecular cyclopropanation to forge the A ring bearing desired stereochemistry at C14; 2) a one-pot borylation/conjugate addition process for creation of the C1-C11 bond; 3) a Wolff ring contraction to assemble the bicyclo[3.2.0]heptane subunit (CD rings); and 4) a stereocontrolled pinacol cyclization for construction of the central B ring of the natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Roberto Serrano, Yaroslav D. Boyko, Lucas W. Hernandez, Aleksandras Lotuzas, David Sarlah
Summary: The concise total syntheses of oxidized norcembranoid terpenoids (-)-scabrolide A and (-)-yonarolide have been achieved in 10 and 11 steps, respectively, by integrating two chiral-pool-derived fragments, including a [5,5]-bicyclic lactone accessed through a powerful Ni-catalyzed pentannulation of functionalized cyclopentenone with methylenecyclopropane and subsequent fragmentation. Additional features included a Liebeskind-Srogl coupling, induction of a cyclization/elimination cascade by a zinc-amido base, and installation of a sensitive enedione motif by latestage ?-oxidation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Joseph P. Tuccinardi, John L. Wood
Summary: This article describes the first total syntheses of the nor-furanocembranoid natural products (+)-ineleganolide and (-)-sinulochmodin C. The synthetic strategy is based on a transannular Michael reaction and a diastereoselective radical cyclization, and discusses the unexpected stereochemical nuances during the evolution and completion of the total synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Raphael J. Zachmann, Kenzo Yahata, Mira Holzheimer, Maxime Jarret, Cornelia Wirtz, Alois Fuerstner
Summary: The structure of prorocentin has been revised through a flexible synthesis approach, showing that the previously proposed structure is incorrect. The new, more plausible structure was obtained using methods such as gold-catalyzed spirocyclization reactions. This study has important implications for the understanding of prorocentin's structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Yingjie Wang, Biao Yu
Summary: The total syntheses of two antiangiogenic anthraquinone glycosides, aturanosides A and B, were achieved in an expeditious manner, emphasizing anthraquinone synthesis, phenol glycosylation, alpha-D-glucosaminoside installation, and judicious use of protecting groups.
Article
Chemistry, Organic
Xinpei Cai, Lei Li, Ye-Cheng Wang, Jianhan Zhou, Mingji Dai
Summary: In this paper, we describe the complete synthesis of phleghenrines A and C from commercially available starting materials in 7 and 8 steps, respectively. Key steps include an inverse electron-demand Diels-Alder reaction between a masked o-benzoquinone and a N-protected enamine to generate a bicyclo[2.2.2]octenone core, a Bu''chner-Curtius-Schlotterbeck one-carbon insertion to expand the bicyclo[2.2.2]octenone to a bicyclo[3.2.2]nonenone, and Trauner's modified 2-pyridone synthesis to install the 2-pyridone moiety.
Article
Chemistry, Organic
Nariyoshi Umekubo, Satoshi Yokoshima
Summary: In this study, the total syntheses of tropolone-containing natural products malettinins C and E were achieved. A nitro compound and a chiral enone were prepared through palladium-mediated nitromethylation and an organocatalyst-mediated asymmetric aldol reaction, respectively, and connected via a Michael reaction. The oxidative dearomatization of a phenol with a cyclic acetal moiety resulted in a spirocyclic dienone, which could be converted into a tropolone through a base-mediated ring-expansion reaction with elimination of the nitro group, providing a pathway to malettinins C and E.
Article
Chemistry, Organic
Joshua M. Nicholson, Glenn C. Micalizio
Summary: Asymmetric de novo syntheses of euphol and tirucallol have been achieved using a concise sequence of chemical steps featuring several modern stereoselective transformations. The preparative solution for these complex natural product synthesis problems departs significantly from biomimetic polyene cyclization chemistry. The syntheses involve various stereoselective reactions to establish tetracyclic structures with stereodefined quaternary centers, providing access to enantiodefined euphane and tirucallane systems.
Article
Chemistry, Multidisciplinary
Gleb A. Chesnokov, Karl Gademann
Summary: Terpenoids are a class of natural compounds with diverse structures and bioactivities, which has attracted significant interest from the chemical community in the past 150 years. The presence of strained small rings in terpenoids makes their chemical synthesis challenging due to limited methods and stability issues. This feature article discusses recent examples of total syntheses of terpenoids with complex carbon frameworks featuring small rings, with a focus on the new developments in strategic and tactical approaches to constructing such systems.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Ming Wang, Ya Wu, Mei Xu, Sheng Liu
Summary: An efficient synthetic route to iheyamine A and its analogues was discovered, involving a crucial one-pot transformation that included C-C migration to form the characteristic seven-membered ring. Subsequent addition of acetone to iheyamine A initiated a cascade process to complete the total synthesis of iheyamine B.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Ming Wang, Ya Wu, Mei Xu, Sheng Liu
Summary: An efficient synthetic route to iheyamine A and its analogues was discovered, involving a crucial one-pot transformation with C-C migration to form the characteristic seven-membered ring. The subsequent addition of acetone to iheyamine A initiated a cascade process leading to the complete total synthesis of iheyamine B.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Linlin Shi, Yingdong He, Jianxian Gong, Zhen Yang
Summary: The efficient palladium-catalyzed decarboxylative cycloaddition process allows for the synthesis of highly substituted delta-lactone and delta-lactam derivatives. This method demonstrates broad substrate scope, good functional group tolerance, and operational convenience, enabling the regioselective access to a variety of lactone and lactam scaffolds in moderate to good yield. The redox-neutral catalytic system promotes the formation of substituted scaffolds with the in situ generation of a cyclic tetra-substituted double bond functionality.
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
Xin-Ting Liang, Bao-Chuan Sun, Nan Zhang, Zhong-Chao Zhang, Yuan-He Li, Qian-Qian Xu, Chang Liu, Jia-Hua Chen, Zhen Yang
Summary: The final phase of the total synthesis of (-)-spirochensilide A is described, utilizing a tungsten-mediated cyclopropene-based Pauson-Khand reaction, intermolecular aldol condensation, and Cu-mediated 1,4-addition to form the desired ring system and stereochemical centers. The developed chemistry will facilitate the synthesis of polycyclic natural products with a unique spiral ring system.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Xin-Ting Liang, Bao-Chuan Sun, Chang Liu, Yuan-He Li, Nan Zhang, Qian-Qian Xu, Zhong-Chao Zhang, Yi-Xin Han, Jia-Hua Chen, Zhen Yang
Summary: A concise and diastereoselective method has been developed for the construction of the key ring system of spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xin-Peng Mu, Yuan-He Li, Nan Zheng, Jian-Yu Long, Si-Jia Chen, Bing-Yan Liu, Chun-Bo Zhao, Zhen Yang
Summary: A novel method for the synthesis of cyclohepta[b]indoles in high yields was developed through a visible-light-induced, photocatalyzed [2+2]-cycloaddition/ retro-Mannich-type reaction of enaminones. Experimental and computational studies indicated that the reaction is initiated by single-electron oxidation of an enaminone moiety, leading to cyclobutane formation and rapid fragmentation in a radical-cation state to produce cyclohepta[b]indoles.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Dian Li, Jinfeng Yang, Bingyan Liu, Jianxian Gong, Zhen Yang
Summary: A strategy for the stereoselective synthesis of desacyl furanmonogones A and B has been achieved, involving key steps such as Fe(ClO4)(3)-mediated oxidative radical cyclization, phosphorane-mediated rearrangement, and Au-catalyzed cascade reaction.
Article
Chemistry, Organic
Feng-Xia Li, Qing-Zhou Zhang, Shi-Jun Li, Guang Lin, Xiang-Yu Huo, Yu Lan, Zhen Yang
Summary: CRV431, a non-immune-suppressive cyclophilin inhibitor, is a clinical candidate for treating NASH and shows potential in treating liver fibrosis and cancer. The compound was synthesized in four steps from commercially available cyclosporine using various chemical reactions.
Article
Chemistry, Organic
Qian Tu, Zheyuan Wang, Zhongchao Zhang, Jun Huang, Zhen Yang
Summary: The structurally intriguing tetracyclic core of complex harziane diterpenoid was successfully constructed in 14 steps from commercially available compound. Key methods used include Mn/Cu-mediated oxidative 1,3-dicarbonyl radical cascade cyclization reaction and Au-catalyzed diastereoselective formal [2 + 2] cycloaddition.
Article
Chemistry, Multidisciplinary
Jun Huang, Tingting Cao, Zhongchao Zhang, Zhen Yang
Summary: The article describes an enantioselective semisynthesis of (-)-bufospirostenin A, involving the use of biomimetic and diastereoselective reactions for construction of the bicyclic motif, and a Co-catalyzed reversible double-bond isomerization reaction for installing the double bond.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Tingting Cao, Lei Zhu, Jun Huang, Zhen Yang
Summary: This study successfully installed a sterically congested all-carbon quaternary center for the first time via a Pd-catalyzed cascade diarylation, providing a new method for the synthesis of complex organic compounds.
Article
Chemistry, Organic
Lijie Zhang, Rongya Wang, Chao Wang, Bingyan Liu, Jinfeng Yang, Zhongchao Zhang, Jun Huang, Zhen Yang
Summary: A spiro-oxepin isoxazoline skeleton was synthesized via 1,3-dipole cycloaddition, enabling the total syntheses of 7-deoxyceratinamide A and 7-deoxypsammaplysins K and O.
Article
Chemistry, Multidisciplinary
Yuan-He Li, Su-Lei Zhang, Yong Lu, Bo Xiao, Tian-Yu Sun, Qian-Qian Xu, Jia-Hua Chen, Zhen Yang
Summary: A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed using bispyrrolidine diboronates(BPDB). Activated by various Lewis or Bronsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions. The catalyst can also distinguish between different binding sites to achieve highly regioselective reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Shu-Min Lu, Chao Chen, Chang Liu, Rudong Liu, Jia-Hua Chen, Zhongchao Zhang, Zhen Yang
Summary: Regioselective synthesis of 5,6,7-trihydroxyl and 5,7,8-trihydroxyl flavones was achieved using a transition-metal-catalyzed C-H oxidation with naturally enriched 5,7-dihydroxyl flavone as the starting material. This method was applied to the synthesis of biologically active flavonoids wogonin, oroxylin A, and their glycosylated derivatives as potential carnitine palmitoyltransferase 1 activators.
Article
Chemistry, Multidisciplinary
Hao-Yuan Liu, Zhen-Yu Zhang, Yi-Ke Zhou, Jia-Hua Chen, Zhen Yang, Yuan-He Li
Summary: This paper presents an efficient strategy for synthesizing the DEFGH rings of phainanoid F, involving a photo-induced electrocyclization and a homoallylic elimination. It is noteworthy that the electrocyclization reaction was used to simultaneously construct two vicinal quaternary carbons in total synthesis, which is a rare example. The strategy outlined here serves as the basis for the total synthesis of Phainanoid F and could be applied in synthesizing other natural products with similar 13,30-cyclodammarane skeletons.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Chemistry, Organic
Zhenyu Zhang, Wei Zhang, Jun-Chen Tang, Jin-Teng Che, Zhongchao Zhang, Jia-Hua Chen, Zhen Yang
Summary: The researchers synthesized (+)-Haperforin G in 20 steps from commercially available starting materials. They used a Co-catalyzed intramolecular Pauson-Khand reaction to selectively construct a cyclopentanone with an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was employed for the convergent and asymmetric cross-coupling of the unstabilized C(sp(3)) radical with an enone. This developed chemistry opens up possibilities for synthesizing structurally diverse analogs of haperforin G (6).
JOURNAL OF ORGANIC CHEMISTRY
(2023)