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)
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)
Article
Chemistry, Organic
Anding Li, Ziru He, Bingyan Liu, Zhen Yang, Zichun Zhang
Summary: In this study, a concise and stereoselective total synthesis of (+/-)-cephanolide B was accomplished in 15 steps. The key steps in the synthesis included an intermolecular Diels-Alder reaction, a tandem reaction featuring intramolecular Pauson-Khand reaction, 6 pi-electrocyclization, and oxidative aromatization to construct the ABC-tricyclic rings (6-5-6), as well as a phthaloyl peroxide-mediated arene oxygenation to install the C-13 phenol group.
Article
Chemistry, Multidisciplinary
Hui Wang, Yi Liu, Hongyuan Zhang, Baochao Yang, Haibing He, Shuanhu Gao
Summary: The asymmetric total syntheses of cephalotaxus C19 diterpenoids, which possess a unique cycloheptene A ring with a chiralmethyl group at C-12, were achieved using a universal strategy. Six members, including previously unreported compounds, were successfully synthesized. The concise approach involved a Nicholas/Hosomi-Sakurai cascade reaction to generate the cycloheptene ring with a chiral methyl group, followed by an intramolecular Pauson-Khand reaction for the construction of the target molecules' complete skeleton. This work provides a new strategy for the synthetic analysis of cephalotaxus diterpenoids and structurally related natural products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Tianhao Ma, Hao Cheng, Mallesham Pitchakuntla, Weihao Ma, Yanxing Jia
Summary: We have achieved the first total synthesis of (-)-principinol C, which is a natural product with an intriguing and complex 5/7/6/5 tetracyclic skeleton and eight contiguous stereocenters. The key step in assembling the 5/7/6/5 tetracyclic skeleton was the intramolecular Pauson-Khand reaction. This synthetic route represents the first application of intramolecular Pauson-Khand reaction of enyne to construct the 7,5-bicyclic ring system in natural product synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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, Multidisciplinary
Yun-Peng Zou, Zheng-Lin Lai, Meng-Wei Zhang, Jianzhao Peng, Shuai Ning, Chuang-Chuang Li
Summary: The first total synthesis of (+/-)- and (-)-daphnilloninB, a daphnicyclidin-type alkaloid with a novel hexa-cyclic core, was achieved through a series of chemical reactions. The B/C/D ring system was efficiently constructed using a mild intramolecular cycloaddition and a GrubbsII catalyst-catalyzed radical cyclization. The E/F fused ring system was synthesized via a diastereo-selective intramolecular Pauson-Khand reaction. The challenging hexa-cyclic core was reassembled from a hexa-cyclic framework found in calyciphylline A-type Daphniphyllum alkaloids through a unique Wagner-Meerwein rearrangement.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Charles J. Dooley, Scott D. Rychnovsky
Summary: The first total synthesis of a norsesquiterpene derived from the Illicium genus is reported. This natural product displays neurotrophic properties and has potential as a therapeutic for neurodegenerative diseases.
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, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
Article
Chemistry, Organic
Dong Whan Jee, Hee-Yoon Lee
Summary: The structural identity of pethybrene was confirmed to be the theoretically proposed 6-5-5 tricyclic structure through total syntheses of two putative structures. Structure 1 was synthesized in 13 steps via Intramolecular Pauson-Khand reaction, while the new proposed structure 2 was obtained from a known [2+2] cycloaddition product in 3 steps.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Organic
Hiroaki Ohno, Shinsuke Inuki
Summary: This review discusses the nonbiomimetic total syntheses of indole alkaloids using alkyne chemistry, highlighting the importance of nonbiomimetic strategies in natural product synthesis and clarifying the differences between nonbiomimetic synthesis and biosynthesis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Ridge Michael P. Ylagan, Eric Jaewon Lee, Daniela E. Negru, Paolo Ricci, Bohyun Park, Haram Ryu, Mu-Hyun Baik, P. Andrew Evans
Summary: We report an enantioselective rhodium(I)-catalyzed Pauson-Khand reaction using 1,6-chloroenynes that contain challenging 1,1-disubstituted olefins. Unlike previous studies, this new approach allows for a wider range of substrates, including both carbon and heteroatom tethers with polar and non-polar substituents on the alkene. DFT calculations reveal the critical role of the halide, which pre-polarizes the alkyne and provides the appropriate steric profile for a favorable interaction with the chiral diphosphine ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Maria Biosca, Daniel Tarr, Oscar Pamies, Montserrat Dieguez
Summary: Pd-catalyzed asymmetric allylic substitution (AAS) is an effective method for producing chiral molecules with alkene-substituted frameworks. Phosphite-oxazolines have emerged as strong candidates to be privileged ligands, providing high enantiocontrol in the Pd-AAS of various substrates and nucleophiles. This review discusses the progress made in the design of tailor-made phosphite-oxazoline ligand libraries for the Pd-AAS and its application in the construction of chiral complex molecules.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Paul Shaw, Storm J. Hassell-Hart, Gayle E. Douglas, Andrew G. Malcolm, Alan R. Kennedy, Gemma White, Laura C. Paterson, William J. Kerr
Summary: In this study, we applied silyl enol ether moieties as efficient alkene coupling partners within cobalt-mediated intramolecular Pauson-Khand reactions. This cyclization strategy delivers valuable oxygenated cyclopentenone products in high yields and allows for the incorporation of a variety of decorated structures.
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, 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
Jiangqun Cheng, Yuan-He Li, Jun Huang, Zhen Yang
Summary: The diastereoselective syntheses of syn- and anti-vicinal dihalides were achieved through an aza Bellus-Claisen rearrangement, involving the reaction of an alpha-chloro carboxylic acid chloride with halogen-substituted trans-allyl morpholines in the presence of Lewis acids. This method was successfully applied to the total synthesis of a group of monoterpene natural products with vicinal dichloride subunits.
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)