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, Organic
Mohammad Z. Abidin, Thangavelu Saravanan, Laura Bothof, Pieter G. Tepper, Andy-Mark W. H. Thunnissen, Gerrit J. Poelarends
Summary: The study presents the asymmetric synthesis of N-arylalkyl-substituted l-aspartic acids using EDDS lyase as a biocatalyst, resulting in products with good enantioselectivity and high yields. This demonstrates that C-N lyases can serve as a powerful synthetic tool for preparing difficult noncanonical amino acids.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Abhilash Rana, Bhanwar Kumar Malviya, Deepak Kumar Jaiswal, P. Srihari, Ajay K. Singh
Summary: This paper presents an approach for chemical synthesis using solar energy, utilizing an integrated programmed solar panel micro-flow platform for Wolff rearrangements to synthesize various compounds. The method does not require a metal catalyst and utilizes sunlight as an energy source, providing a greener and more efficient approach.
Article
Chemistry, Multidisciplinary
Fuzhuo Li, Li-Cheng Yang, Jingyang Zhang, Jason S. Chen, Hans Renata
Summary: A highly diastereo- and enantioselective biocatalytic transamination method was developed for the preparation of a broad range of aromatic beta-branched alpha-amino acids. The transformation proceeds through dynamic kinetic resolution unique to the optimal enzyme, showcasing its utility for the synthesis of sp(3)-rich cyclic fragments and total synthesis of jomthonic acid A.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Cong Fu, Qi Xiong, Lu Xiao, Ling He, Tian Bai, Zongpeng Zhang, Xiu-Qin Dong, Chun-Jiang Wang
Summary: This article proposes a novel approach to the stereodivergent synthesis of carbocyclic alpha-quaternary amino acid derivatives through sequential dual Cu/Ir-catalyzed asymmetric allylation and ring-closing metathesis. The method exhibits high yields, exclusive regioselectivities, and excellent diastereoselectivities and enantioselectivities. Furthermore, it is capable of synthesizing challenging seven and eight-membered carbocyclic alpha-amino acid derivatives.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ling Zhao, Yicong Luo, Junzhe Xiao, Xiaohong Huo, Shengming Ma, Wanbin Zhang
Summary: The stereodivergent synthesis of allene compounds with adjacent chiralities has been achieved through Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation. The matched reactivity of a bimetallic catalytic system allows for a smooth reaction of racemic aryl-substituted allenylic acetates with sterically crowded aldimine esters. Various chiral non-natural amino acids with a terminal allenyl group can be easily synthesized with high yields and excellent diastereo- and enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Youbin Peng, Chongyu Han, Yicong Luo, Guanlin Li, Xiaohong Huo, Wanbin Zhang
Summary: The first asymmetric Ni/Cu cocatalyzed benzylation of aldimine esters is reported, allowing the synthesis of benzyl-substituted alpha-quaternary amino acids in high yield and with high enantioselectivity. The strong electrophilicity of the eta(3)-benzylnickel intermediate was found to be crucial for the high reactivity, enabling the reaction under base-free conditions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Rosa Lopez, Claudio Palomo
Summary: N,N-Diacylaminals are flexible molecular scaffolds commonly used as amide surrogates in peptidomimetics. Recently, their singularity as an N-acyl imine equivalent and hydrogen-bond donor has led to new synthetic opportunities, particularly in the field of asymmetric catalysis. This concept article highlights the diverse synthetic potential of N,N-Diacylaminals and provides the necessary elements for further developments.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Dana Mustafa, Justin M. Overhulse, Boris A. Kashemirov, Charles E. McKenna
Summary: Phosphonic acids are important organophosphorus compounds widely used in various fields. A convenient and efficient method for the preparation of phosphonic acids is silyldealkylation with bromotrimethylsilane (BTMS), followed by desilylation. We investigated microwave irradiation as an acceleration method for BTMS reactions and found that it had significant advantages over conventional heating, including higher yields and chemoselectivity. This method was also applied to the preparation of antiviral and anticancer drugs, showing great potential.
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
Dominik Albat, Martin Reiher, Joerg-Martin Neudoerfl, Hans-Guenther Schmalz
Summary: A new class of chiral C-2-symmetric diphosphines (MediPhos) has been shown to be highly effective in the Pd-catalyzed asymmetric N-allylation of amino acid esters. A new and improved method for preparing these ligands through bidirectional S(N)2-coupling has been described, providing access to nine ligands with branched alkyl substituents, which exhibited excellent performance in enantioselective Pd-catalyzed N-allylation reactions. Additionally, the synthesized allylic amines were utilized in the stereoselective synthesis of conformationally restricted dipeptide analogs.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Erick Martinez-Toto, Mario Ordonez, Juan C. Morales-Solis, Marcos Flores-Alamo
Summary: The diastereoselective synthesis of (2S,5R)-5-methyl-5-(phosphono)-proline, a phosphoproline derivative from L-pyroglutamic acid, is reported. The key feature of this method is the use of chiral cyclic imines as intermediates and the selective nucleophilic addition of phosphites. The target compound is obtained through cleavage and hydrolysis reactions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Michal G. Nowak, Andrzej S. Skwarecki, Maria J. Milewska
Summary: The structures of many antibacterial, antifungal, or antiprotozoal agents are based on amino acid scaffolds. The amino acid skeleton is crucial for their antimicrobial activity, particularly in the case of aminophosphonate or aminoboronate analogs. The synthesis of amino acid antimicrobials presents a specific challenge, especially in terms of enantioselective methods.
Article
Chemistry, Multidisciplinary
Bastian Jakob, Andreas M. Diehl, Kathrin Horst, Harald Kelm, Georg Manolikakes
Summary: Here we report a palladium-catalyzed asymmetric three-component synthesis of α-arylglycine derivatives. This operationally simple method utilizes glyoxylic acid, sulfonamides, and arylboronic acids as starting materials to obtain α-arylglycine scaffold in good yields and enantioselectivities. The synthesized products can be directly used as building blocks in peptide synthesis.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shi-Jing Zhai, Dominique Cahard, Fa-Guang Zhang, Jun-An Ma
Summary: Three bench-stable difluoromethylene phosphonate hydrazones were synthesized in good yields from simple diethyl(difluoromethyl)phosphonate within two steps. The [3 + 2] cycloaddition reaction with aryl diazonium salts under metal-free conditions exhibited exclusive regioselectivity. This method provides practical access to a wide range of 2-aryl-2H-tetrazol-5-yl difluoromethylene phosphonates, including derivatives of amino acids and drug cores.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Maxime Manneveau, Batoul Rkein, Dominique Cahard, Julien Legros, Isabelle Chataigner
Summary: This study demonstrates that indoles substituted by electron-depleted thio groups at positions 1 and 3 can react as C2 = C3 dipolarophiles with an electron-rich azomethine ylide dipole under flow conditions, leading to dearomatizing (3 + 2) cycloadditions to afford the corresponding fluorinated 3D-pyrrolidinoindolines bearing a tetrasubstituted carbon centre at the ring junction.
JOURNAL OF FLOW CHEMISTRY
(2022)
Article
Chemistry, Organic
Lucas Popek, Thi Mo Nguyen, Nicolas Blanchard, Dominique Cahard, Vincent Bizet
Article
Chemistry, Organic
Yuji Sumii, Hiroto Iwasaki, Yamato Fujihira, Elsayed M. Mahmoud, Hiroaki Adachi, Takumi Kagawa, Dominique Cahard, Norio Shibata
Summary: A protocol for the stereodivergent pentafluoroethylation of N-sulfinylimines has been developed using HFC-125 with KHMDS/triglyme. The presence or absence of triglyme enables the selective synthesis of both diastereomers of the pentafluoroethylated amines. This additive-controlled protocol offers a straightforward and cost-effective alternative to the previously reported base-controlled stereodivergent trifluoromethylation using potassium hexamethyldisilazide (KHMDS) versus P4-tBu.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Ziwei Luo, Dominique Cahard, Gavin Chit Tsui
Summary: This article summarizes the latest research reports on the application of fluoroform in organic synthesis since 2017, including direct trifluoromethylation facilitated by organic and inorganic bases, preparation of trifluoromethylation reagents based on transition metals and borazine, and radio-labeled fluoroform.
JOURNAL OF FLUORINE CHEMISTRY
(2023)
Article
Chemistry, Organic
Ye Yuan, Muliang Zhang, Xiaodong Tang, Jared L. Piper, Zhi-Hui Peng, Jun-An Ma, Jie Wu, Fa-Guang Zhang
Summary: We have developed a photoredox platform that utilizes sulfinate as a radical-relay precursor and a sacrificial nucleofuge, allowing for the construction of styrenyl polyfluoro (hetero)arenes with branch selectivity. This protocol combines photoredox catalysis, radical-radical coupling, and an elimination process in a one-pot operation, providing a mild and efficient method to access polyfluoro (hetero)aryl derivatives of natural products and drugs.
Article
Chemistry, Multidisciplinary
Norio Shibata, Dominique Cahard
Summary: From 2000, our two research groups independently and simultaneously designed and developed a novel family of electrophilic fluorinating reagents based on the use of Cinchona alkaloids. The chiral N-fluoro ammonium salts demonstrated the highest efficiency compared to prior art in enantioselective electrophilic fluorination for a wide range of substrates. In this account, we tell our respective stories, how the same idea germinated in our laboratories, the characterization of the chiral reagents, the use in stoichiometric quantity then the development of a catalytic version, the application to the synthesis of chiral fluorinated molecules of pharmaceutical interest, and finally the exploitation of our reagents by other teams and for other applications.
Article
Chemistry, Medicinal
Thibault Alle, Sipak Joyasawal, Killian Oukoloff, Keith Long, Zachary Owyang, Karol R. Francisco, Dominique Cahard, Donna M. Huryn, Carlo Ballatore
Summary: In this study, fluorinated alcohols and phenols were investigated as bioisosteres of the carboxylic acid functional group. A structure-property relationship analysis was conducted using matched molecular pair analyses to compare their properties with other commonly used non-fluorinated bioisosteres. Physicochemical properties, such as acidity, lipophilicity, and permeability, were experimentally determined for representative examples. The results provide insights into the relative changes in physicochemical properties achievable by replacing the carboxylic acid functional group with fluorine-containing surrogate structures.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Tao-Qian Zhao, Hui Xu, Yu-Chen Tian, Xiaodong Tang, Yanfeng Dang, Shaozhong Ge, Jun-An Ma, Fa-Guang Zhang
Summary: In this study, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high regio- and enantioselectivities is reported. The use of a native carbonyl directing group, copper hydride system, and bisphosphine ligand plays a crucial role in suppressing fluoride elimination and achieving the desired selective hydroboration. This atom-economic protocol provides a practical and efficient synthetic platform for the preparation of chiral secondary boronates containing difluoromethylene motifs.
Article
Chemistry, Multidisciplinary
Masa Sterle, Martina Durcik, Clare E. M. Stevenson, Sara R. Henderson, Petra Eva Szili, Marton Czikkely, David M. Lawson, Anthony Maxwell, Dominique Cahard, Danijel Kikelj, Nace Zidar, Csaba Pal, Lucija Peterlin Masic, Janez Ilas, Tihomir Tomasic, Andrej Emanuel Cotman, Anamarija Zega
Summary: We have developed a new series of DNA gyraseB inhibitors based on 2-aminobenzothiazole, showing promising activity against ESKAPE bacterial pathogens. The chemical space of the benzothiazole-based series was expanded to the C5 position of the benzothiazole ring, resulting in compound E with low nanomolar inhibition of DNA gyrase and broad-spectrum antibacterial activity. Computational analysis revealed that substitution at position C5 can enhance the inhibitory potency of the compounds and modify their physicochemical properties.
Editorial Material
Chemistry, Physical
Nicolas Marie, Dominique Cahard
Article
Chemistry, Organic
Nan Zhang, Hai Ma, Chi Wai Cheung, Fa-Guang Zhang, Marcin Jasinski, Jun-An Ma, Jing Nie
Summary: Here, we report a base-mediated [3 + 2] cycloaddition reaction between di/trifluoromethylated hydrazonoyl chlorides and fluorinated nitroalkenes. This reaction provides a direct and easy approach to incorporate both a fluorine atom and fluoroalkyl group into pyrazole cores, leading to the synthesis of a diverse range of densely functionalized 3-di/trifluoroalkyl-5-fluoropyrazoles with high yields and excellent regioselectivities. Moreover, several drug-like 3-di/trifluoroalkyl-5-fluoropyrazoles have been synthesized and shown to exhibit potent inhibitory activities against cyclooxygenase 2 (COX-2).
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zhi-Qi Zhang, Cheng-Qiang Wang, Long-Ji Li, Jared L. Piper, Zhi-Hui Peng, Jun-An Ma, Fa-Guang Zhang, Jie Wu
Summary: This study presents an efficient and modular protocol for synthesizing difluorinated compounds using readily accessible ClCF2SO2Na as a versatile difluoromethylene linchpin. Various difluorinated compounds were successfully obtained with satisfactory yields, including gem-difluoroalkanes, gem-difluoroalkenes, difluoromethyl alkanes, and difluoromethyl alkenes. The practical utility of this method was demonstrated through the successful preparation of CF2-linked derivatives of complex drugs and natural products. This method opens up new avenues for synthesizing structurally diverse difluorinated hydrocarbons and highlights the utility of ligated boryl radicals in organofluorine chemistry.
Article
Chemistry, Multidisciplinary
Cheng-Feng Gao, Yue-Ji Chen, Jing Nie, Fa-Guang Zhang, Chi Wai Cheung, Jun-An Ma
Summary: Here, we describe a [2+1] annulation reaction between di/trifluorodiazoethane and (alkylidene)malononitriles. This reaction offers an efficient synthesis of stereospecific and densely functionalized difluoromethyl and trifluoromethyl cyclopropane-1,1-dicarbonitriles. Further reactions allow for the conversion to structurally distinct cyclopropyl compounds.
CHEMICAL COMMUNICATIONS
(2023)
