Article
Chemistry, Multidisciplinary
Jinzheng Wang, Du'an Lin, Ming Liu, Han Liu, Pilar Blasco, Zhenquan Sun, Yan Chu Cheung, Sheng Chen, Xuechen Li
Summary: By streamlining solution phase-solid phase synthesis and chemical ligation-mediated peptide cyclization, the total synthesis of mannopeptimycin beta was achieved. Mannoeloptimycin beta, a cyclic glycopeptide, exhibits antibacterial activity against antibiotic-resistant Gram-positive pathogens.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Arianna Quintavalla, Davide Carboni, Maria Simeone, Marco Lombardo
Summary: An efficient enantioselective synthesis of chiral alpha-disubstituted beta-homoprolines was developed by utilizing the stereodivergent allylation reaction of chiral N-tert-butanesulfinyl imines derived from 4-bromobutanal with indium or zinc catalysts. This methodology allows for easy introduction of different substituents at the alpha-position of the pyrrolidine scaffold and offers the flexibility to switch the absolute configuration of the newly formed stereocenter by altering the chiral auxiliary or the allylation protocol.
Article
Chemistry, Organic
Arianna Quintavalla, Davide Carboni, Maria Simeone, Marco Lombardo
Summary: An efficient enantioselective synthesis of chiral alpha-disubstituted beta-homoprolines has been developed, allowing for easy introduction of different substituents at the alpha-position and switching of the stereocenter's absolute configuration.
Article
Chemistry, Organic
Jacob Soley, Scott D. Taylor
Summary: The synthesis of beta-hydroxy-alpha,alpha-difluorosulfonamides was achieved by reacting difluoromethanesulfonamides with KHMDS in the presence of an aldehyde or ketone. The reaction showed a significant counterion effect with KHMDS or NaHMDS providing excellent yields, while lithium bases did not give much product. The use of N-alpha-benzyl-N-alpha-phenylfluorenyl (PhF)-protected chiral amino aldehydes derived from amino acids resulted in excellent yields and high diastereomeric ratios. Following deprotection, a beta-hydroxy-alpha,alpha-sulfonamide reacted under peptide coupling and Mitsunobu conditions to produce a peptidomimetic compound with a high overall yield.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Meiqi Li, Yiming Liu, Huiyu Si, Xin Zhou, Yong Jian Zhang
Summary: The first enantioselective total synthesis of aryltetralin lignan acetals, along with their enantiomers, has been accomplished using Pd-catalyzed asymmetric allylic cycloaddition as a key step. In vitro cytotoxicity against several cancer cells has been preliminarily examined for the obtained six stereoisomers of lignan acetals.
Article
Chemistry, Organic
Peng Zou, Hongjian Yang, Jian Wei, Taimin Wang, Hongbin Zhai
Summary: The first asymmetric total synthesis of three picrinine-type akuammiline alkaloids has been achieved, involving an efficient acid-promoted oxo-bridge ring-opening, an unusual Dauben-Michno oxidation, and a nickel-mediated reductive Heck reaction to forge the [3.3.1]-azabicyclic core.
Article
Chemistry, Organic
Toshimichi Kobayashi, Soshi Nishino, Masahiro Miura, Koji Hirano
Summary: A copper-catalyzed silylamination reaction has been developed for the synthesis of β-silyl-α-amino acid derivatives, which are of great interest in medicinal and pharmaceutical chemistry. The use of a suitable chiral ligand enables asymmetric induction, leading to the formation of optically active compounds with high enantiomeric ratios.
Article
Chemistry, Organic
Erwann Grenet, Pierre-Yves Geant, Xavier J. Salom-Roig
Summary: Crystallization-Induced Diastereomer Transformation (CIDT) is used to synthesize enantiopure alpha-bromoketones, which can then be further transformed into valuable anti and syn-bromohydrins with excellent diastereoselectivities. CIDT is also applied in the diastereodivergent synthesis of enantiopure hemlock alkaloids.
Article
Chemistry, Multidisciplinary
Aibo Li, Xinjian Song, Qiao Ren, Peiwang Bao, Xinyu Long, Fuli Huang, Lvjiang Yuan, Jianrong Steve Zhou, Xurong Qin
Summary: A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol resulted in the synthesis of highly enantioselective α,β-dideuterio-α-amino esters with almost complete deuteration (99%). This new protocol was successfully employed for the preparation of dideuterio-α-amino acid fragments in certain drugs, and also applied in the concise synthesis of dideuterio L-DOPA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Soshi Nishino, Yuji Nishii, Koji Hirano
Summary: A copper-catalyzed reaction has been developed for the regio- and diastereoselective borylamination of alpha,beta-unsaturated esters with B(2)pin(2) and hydroxylamines. The reaction delivers acyclic beta-boryl-alpha-amino acid derivatives with high anti-diastereoselectivity, which is difficult to achieve using established methods. Furthermore, the use of a chiral phosphoramidite ligand allows for the enantioselective synthesis of optically active beta-borylated alpha-amino acids. The resulting products can be further transformed into beta-functionalized alpha-amino acids, which are of great interest in medicinal chemistry.
Article
Chemistry, Multidisciplinary
Jairo Villalona, Peyton M. Higgins, Andrew R. Buller
Summary: Non-canonical amino acids (ncAAs) serve as useful materials for developing new medicines, materials, and bioactive probes. In this study, the beta-subunit of tryptophan synthase, TrpB, was engineered through directed evolution to improve its activity with diverse amine nucleophiles. Mechanistic analysis revealed hindrance to high yields due to product re-entry and subsequent decomposition. Additional equivalents of l-serine were able to inhibit product re-entry through kinetic competition, facilitating preparative scale synthesis. Several beta-substituted amino acids were synthesized using a variety of aryl amine nucleophiles, including demonstration on a gram scale. These amino acids represent an underexplored class of building blocks for chemical biology and medicinal chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jairo Villalona, Peyton M. Higgins, Andrew R. Buller
Summary: In this study, directed evolution was used to engineer the beta-subunit of tryptophan synthase for improved activity in the synthesis of beta-substituted amino acids. Mechanistic analysis revealed that product re-entry into the catalytic cycle and subsequent decomposition hindered high yields, but additional equivalents of l-serine could inhibit product re-entry and facilitate preparative scale synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Chen Chen, Jun Ge, Ling He
Summary: In this study, alpha,beta-unsaturated gem-diazides were selectively synthesized using Yb(TfO)(3) as a catalyst and alpha,beta-unsaturated aldehydes as substrates. The obtained compounds showed potential for synthesis of other organic compounds and exhibited promising anticancer activity.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Lukas Fliegel, Jens Christoffers
Summary: Reacting beta-oxoesters with PIFA yields alpha-(iodophenyl) derivatives, which serve as starting materials for the preparation of [b] annulated benzofurane derivatives through copper-catalyzed C-O coupling reaction. The resulting scaffold shows great potential in medicinal chemistry and can be diversified to obtain various structurally different compounds.
Article
Chemistry, Physical
Guowei Kang, Daniel Romo
Summary: A photochemical, beta-selective hydrogenation of alpha, beta-unsaturated esters using CO2 radical anion under flow conditions was developed. The reaction tolerated various substrates with different functional groups and resulted in a series of quaternary carboxylic acids. Mechanistic studies suggest a Giese-type CO2 radical anion conjugate addition followed by hydrogen atom transfer as the main reaction pathway, and a telescoped process for beta-lactone synthesis.
Article
Chemistry, Multidisciplinary
Quanquan Wang, Wanjun Zhu, Qikai Sun, Gang He, Gong Chen
Summary: A novel Pd-catalyzed ortho-directed C-H glycosylation reaction using N-linked bidentate auxiliaries has been developed for efficient synthesis of C-aryl glycosides with high yield and selectivity. This method allows for installation of a wide range of pyranose and furanose moieties on various substrates and facile installation and removal of the auxiliaries under mild conditions.
CHINESE JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zibo Bai, Heng Zhang, Hao Wang, Hanrui Yu, Gong Chen, Gang He
Summary: An enantioselective addition reaction of various alkyl groups to unactivated internal alkenes under Cu catalysis has been developed, leading to high yields of β-lactams featuring two contiguous stereocenters with excellent enantioselectivity. Mechanistic studies suggest that a nucleophilic addition of the alkyl radical to Cu-II-coordinated alkene is the enantio-determining step.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Xiafei Hu, Xiangxiang Chen, Bo Li, Gang He, Gong Chen
Summary: New methods have been developed in this study to construct peptide macrocycles via radical-mediated intramolecular C-H alkylation reactions under photoredox catalysis, providing a new strategy for the synthesis of complex peptide macrocycles.
Article
Chemistry, Multidisciplinary
Hao Wang, Hoimin Jung, Fangfang Song, Shiyang Zhu, Ziqian Bai, Danye Chen, Gang He, Sukbok Chang, Gong Chen
Summary: N-N linkages are important in natural compounds, and a nitrene-mediated intermolecular N-N coupling reaction using iridium or iron catalysis provides a simple and efficient method to synthesize various hydrazides from readily available carboxylic acid and amine precursors. Mechanistic studies show that the nitrogen atom of Ir acyl nitrene intermediates serves as a strong electrophile and can form N-N bonds with high efficiency and chemoselectivity with the assistance of Cl···HN hydrogen bonding.
Article
Chemistry, Multidisciplinary
Wanjun Zhu, Qikai Sun, Hai Chang, Hui-Xing Zhang, Quanquan Wang, Gong Chen, Gang He
Summary: A new protocol for the synthesis of 2-deoxy-C-aryl-glycosides and 2-deoxy-C-alkyl-glycosides via iridium-catalyzed directed C-H glycosylation with glycals is reported. The benzoxazole directing group can be cleanly removed by the treatment of KOH or LiAlH4, offering a versatile method for the synthesis of these glycosides.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Bo Li, Lan Wang, Xiangxiang Chen, Xin Chu, Hong Tang, Jie Zhang, Gang He, Li Li, Gong Chen
Summary: In this study, a method for macrocyclization of two free-amine-containing residues in mild conditions is disclosed. This method can efficiently generate complex peptide structures, expanding the toolbox for peptide chemistry.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Shaokun Cai, Qikai Sun, Quanquan Wang, Gang He, Gong Chen
Summary: Metal-catalyzed C-H glycosylation reactions are important strategies for the synthesis of C-glycosides. This study developed a new ruthenium catalyst for the ortho C-H glycosylation of arenes with various glycosyl chloride donors using a monodentate pyridine directing group.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ziqian Bai, Shiyang Zhu, Yiyao Hu, Peng Yang, Xin Chu, Gang He, Hao Wang, Gong Chen
Summary: This study reports a method for the synthesis of N-acyl sulfenamides via copper-catalyzed S-amidation of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. The resulting N-acetyl sulfenamides can be used as highly effective S-sulfenylation reagents and enable the synthesis of sterically demanding disulfides that are difficult to prepare by other means.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Xin Chu, Bo Li, Hao-Yang Liu, Xiaowei Sun, Xiaochen Yang, Gang He, Chuanzheng Zhou, Weimin Xuan, Shu-Lin Liu, Gong Chen
Summary: In this study, a simple and powerful method for bioconjugation is reported, using ortho-phthalaldehyde (OPA) reagent to efficiently and selectively crosslink various alpha-amino acids, aryl amines, and secondary amines to the epsilon-amino side chain of lysine on peptides or proteins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yaxin Wang, Zehui Cao, Qin He, Xin Huang, Jiaxi Liu, Helfried Neumann, Gong Chen, Matthias Beller
Summary: A simple and efficient method has been developed for activating perfluoroalkyl iodides using tBuONa or KOH, without the need for expensive photo- or transition metal catalysts. This method enables various transformations including alpha-sp(3) C-H amidation reactions of alkyl ethers and benzylic hydrocarbons, C-H iodination of heteroaryl compounds, and perfluoroalkylations of electron-rich pi bonds. Mechanistic studies have shown that these reactions are mediated by halogen bond interactions between perfluoroalkyl iodides and tBuONa or KOH, leading to the homolysis of perfluoroalkyl iodides under mild conditions.
Article
Chemistry, Multidisciplinary
Peng Yang, Martynas J. Sirvinskas, Bo Li, Nicholas W. Heller, Hua Rong, Gang He, Andrei K. Yudin, Gong Chen
Summary: In this study, a broadly applicable strategy to remodel the structure of homodetic peptides by cross-linking the aromatic side chains of Trp, His, and Tyr residues with various aryl linkers is reported. The aryl linkers can be easily installed via copper-catalyzed double heteroatom-arylation reactions of peptides with aryl diiodides. These aromatic side chains and aryl linkers can be combined to form a large variety of assemblies of heteroatom-linked multi-aryl units. The assemblies can serve as tension-bearable multi-joint braces to modulate the backbone conformation of peptides as an entry to previously inaccessible conformational space.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Applied
Qin He, Zehui Cao, Yangyang Zhang, Gong Chen, Yaxin Wang
Summary: A novel radical reaction system mediated by azidobenziodoxole (BIN3) was developed for selective chlorination and bromination of tertiary and secondary C(sp(3)) H bonds of alkyl substrates using haloform as the halogen donor. The reactions of various substrates with BIN3 under visible light irradiation yielded C-H chlorinated or brominated products without the need for any photo or metal catalysts. The mechanism involves haloform serving as the halogen atom donor and HN3 generated in situ from the reaction of BIN3 and water as the hydrogen atom donor, which propagate a radical chain reaction by abstracting a hydrogen atom from the alkane substrate.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Multidisciplinary Sciences
Yifei Zhou, Hongjun Li, Yi Huang, Jiahui Li, Guiyu Deng, Gong Chen, Zhen Xi, Chuanzheng Zhou
Summary: During solid-phase peptide synthesis (SPPS), the main side reactions of protected amino acids are hard to remove. The authors here report a thiol-labile amino protecting group, DNPBS, which greatly suppresses these side reactions observed in conventional SPPS. Although DNPBS SPPS is less efficient than Fmoc SPPS, they can be combined to synthesize peptides that are otherwise difficult to obtain.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Shi-Yang Zhu, Wen-Ji He, Guan-Chi Shen, Zi-Qian Bai, Fang-Fang Song, Gang He, Hao Wang, Gong Chen
Summary: In this work, we demonstrate that bulky alkylphosphines such as PtBu3 can switch from being active ligands to being spectator ligands, promoting the FeCl2-catalyzed N-amidation reaction of arylamines with dioxazolones to yield hydrazides with high efficiency and chemoselectivity. Mechanistic studies show that the phosphine ligands can enhance the decarboxylation of dioxazolones on the iron center, and hydrogen bonding interactions between the arylamines and the ligands on Fe nitrenoid intermediates might play a role in tuning the delicate interplay between phosphine ligand, arylamine, and acyl nitrene N, thereby favoring N-N coupling over N-P coupling. The ligand-promoted N-amidation protocols presented here provide a convenient approach to access various challenging triazane compounds through double or sequential N-amidation of primary arylamines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Yaxin Wang, Qin He, Zehui Cao, Peng Wang, Gong Chen, Matthias Beller
Summary: This study reports a visible-light-promoted and radical-mediated strategy for the site-specific cleavage of C(sp(3))-C(sp(3)) bonds in ethers. Different cyclic and linear alkyl ethers can be converted into benzoylated acetals and aldehydes or ketones under mild conditions in the presence of Ru(bpy)(3)Cl-2 as a photocatalyst and Zhdankin's lambda(3)-azidoiodane reagent, with moderate to high yields. Control experiments and mechanistic investigations provide a plausible mechanism for this unusual deconstructive esterification of ethers.
ORGANIC CHEMISTRY FRONTIERS
(2022)
