Article
Chemistry, Organic
Yasushi Yoshida, Reina Kasuya, Takashi Mino, Masami Sakamoto
Summary: The first phase-transfer catalyzed asymmetric synthesis of alpha-chiral tetrasubstituted alpha-aminothioesters has been reported in this study, affording products with up to 81% ee. This work fills a gap in the limited existing literature on the asymmetric synthesis of these important scaffolds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Minjie Zhang, Peng Cui, Kai Zhang, Zhen Shi, Xu Cheng, Xiang Ji, Hao Song, Bowen Ke, Yong Qin
Summary: An efficient method for the Ir-catalyzed asymmetric hydrogenation of tetrasubstituted alpha-acylpyrazole-beta-alkyl cycloalkenes has been developed, affording 1,2-cis substituted carbo- or heterocycles with high yields and excellent enantioselectivities.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Caria Evans, William J. Berkey, Christopher W. Jones, Stefan France
Summary: A Zr-catalyzed synthesis of tetrasubstituted 1,3-diacylpyrroles has been reported using N-acyl alpha-aminoaldehydes and 1,3-dicarbonyl compounds. The reaction showed high yields (up to 88%) and the products were found to be hydrolytically and configurationally stable. The N-acyl alpha-aminoaldehydes were easily prepared from corresponding alpha-amino acids. The reaction could accommodate various substrate types and a range of 1,3-dicarbonyls, including aldehyde derived from a l,l-dipeptide, an in situ generated aldehyde, and an N-acylated glucosamine.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Peng-Wei Xu, Xiao-Yuan Cui, Chen Chen, Feng Zhou, Jin-Sheng Yu, Yu-Fei Ao, Jian Zhou
Summary: This study describes an unprecedented catalytic enantioselective cyanation of ketonitrones using a bifunctional cyanating reagent, Me-2(CH2Cl)SiCN, leading to the synthesis of optically active N-hydroxyl-alpha-amino nitriles. The use of this reagent not only achieves high enantioselectivity but also allows for diversification reactions of the resulting silylated adducts. Additionally, this work highlights the potential of tetrasubstituted C.N bonds for asymmetric synthesis of N-hydroxy alpha-amino acids and other N-hydroxy tertiary amines.
Article
Chemistry, Multidisciplinary
Jialing Zhong, Rihuang Pan, Xufeng Lin
Summary: An enantioselective Friedel-Crafts reaction of cyclic alpha-diaryl N-acyl imines with indolizines catalyzed by a chiral spirocyclic phosphoric acid has been developed, leading to the synthesis of alpha-tetrasubstituted (3-indolizinyl) (diaryl)methanamines with high enantioselectivity under mild conditions.
Article
Chemistry, Organic
Feng Zhou, Qi-Long Hu, Ke-Qiang Hou, Albert S. C. Chan, Xiao-Feng Xiong
Summary: A convenient strategy for the diastereoselective synthesis of alpha,beta-diamino diacid derivatives bearing congested vicinal acyclic tetrasubstituted stereocenters via catalytic Mannich-type reactions of azlactones and 2-aminoacrylates was established. A diverse set of alpha,beta-diamino diacid derivatives were synthesized in good to excellent yields and diastereoselectivities. Good enantioselectivity (up to 98:2 er) was achieved by employing the catalyst (DHQD)2PHAL in the subsequent asymmetric study.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Alejandro Torregrosa-Chinillach, Asier Carral-Menoyo, Enrique Gomez-Bengoa, Rafael Chinchilla
Summary: A highly efficient enantioselective alpha-nitrogenation method has been developed for synthesizing alpha,alpha-disubstituted alpha-nitrogenated aldehydes without the need for any solvents, achieving high yields and excellent enantioselectivities. The sustainability and rationality of the method have been demonstrated through green metrics calculation and theoretical calculations.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Takayuki Katoh, Hiroaki Suga
Summary: The study demonstrates the feasibility of multiple and consecutive incorporations of alpha-aminoxy/alpha-hydrazino acids with different configurations into peptides during ribosomal translation, including macrocyclic peptide scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Fei Zhao, Jin Qiao, Yangbin Lu, Xiaoning Zhang, Long Dai, Xin Gong, Hui Mao, Shiyao Lu, Xiaowei Wu, Siyu Liu
Summary: In this study, alkynylated imidazo[1,5-a]indoles and alpha,alpha-difluoromethylene tetrasubstituted alkenes were successfully synthesized via Rh(III)-catalyzed [4 + 1] annulation/alkyne moiety migration and C-H alkenylation/DG migration, showing excellent product selectivity, high yields, and good tolerance of functional groups.
Article
Biochemistry & Molecular Biology
Raja Banerjee, Tridip Sheet, Srijan Banerjee, Barbara Biondi, Fernando Formaggio, Claudio Toniolo, Cristina Peggion
Summary: In synthetic peptides, incorporating a large number of L-Ala residues and noncoded Aib units enhances their helical extent, but the achiral nature of Aib poses challenges in analyzing their helical conformations. By replacing Aib with L-AMV, it is found that the L-AMV-containing peptide exhibits a significantly stronger preference for alpha-helical character compared to its Aib parent. L-AMV, as a chiral amino acid, shows an intrinsic bias for a specific (right-handed) screw sense, emphasizing its relevance for designing right-handed alpha-helical peptide models.
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
Hao Jia, Tobias Ritter
Summary: In this study, we report the synthesis of an alpha-thianthrenium carbonyl species, which serves as the equivalent of an alpha-carbonyl carbocation. This species is generated through radical conjugate addition and exhibits distinct reactivity compared to traditional methods. The reactivity allows for the synthesis of C-alpha-tetrasubstituted alpha- and beta-amino acid analogues via a Ritter reaction, as well as the synthesis of alpha-heteroatom substituted alpha-phenylpropanoates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Saikat Pahan, Sanjit Dey, Gijo George, Souvik Panda Mahapatra, DRGKoppalu R. Puneeth Kumar, Hosahudya. N. Gopi
Summary: In this study, chiral beta-double helices constructed from specific amino acids were observed in both single crystals and in solution. These structures can transport ions across membranes, suggesting their potential applications in designing functional foldamers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Gangarajulu Kesavulu, Biguvu Balachandra, Kavirayani R. Prasad
Summary: The use of lithio tris(methylthio)methane as an anion equivalent enables the synthesis of α-amino acids. Reactions with nonracemic sulfinimines yield α-sulfinamido trithioformates with excellent diastereoselectivity. Conversion of trithioformates to diverse functionalities such as α-amino acid thioesters, esters, anilides, amides, and di/tripeptides is achieved without epimerization of chiral centers.
Article
Polymer Science
Jingcheng Zou, Min Zhou, Zhemin Ji, Ximian Xiao, Yueming Wu, Ruxin Cui, Shuai Deng, Runhui Liu
Summary: This study presents a novel method for the synthesis of peptide/peptoid hybrid polymers with alternating distribution of residues, controlled molecular weight, and narrow dispersity. This method allows for quick synthesis of peptide mimicking peptide/peptoid hybrid polymers with adjustable proteolysis and opens up new possibilities for preparing novel peptide mimics with tunable proteolysis and large structural diversity.
Article
Chemistry, Multidisciplinary
Steven M. Wales, David T. J. Morris, Jonathan Clayden
Summary: Ethylene-bridged oligoureas with a continuous, switchable chain of hydrogen bonds and a binding site for a hydrogen-bond-accepting ligand were synthesized. The polarity and ligand binding ability of these oligomers can be controlled remotely through a deprotonation/reprotonation cycle. Conformational changes induced by base addition can release the ligand, while reprotonation restores the function of the binding site.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Nicola Forlano, Raffaella Bucci, Alessandro Contini, Mariano Venanzi, Ernesto Placidi, Maria Luisa Gelmi, Raffaella Lettieri, Emanuela Gatto
Summary: This study describes the self-assembly properties of an alpha,beta-peptide, which can self-organize into a fascinating supramolecular rope on surfaces. The material was characterized by AFM, electronic conduction and fluorescence measurements. Molecular dynamics simulations showed that this peptide can self-assemble into an antiparallel beta-sheet layer, which can further self-assemble into many side-by-side layers. The presence of aromatic residues promoted by the alternation of alpha,beta-amino-acids in the primary sequence endorses the formation of a super-secondary structure with good electron conduction properties.
Article
Chemistry, Organic
Giorgio Facchetti, Jaime Gracia Vitoria, Martina Moraschi, Raffaella Bucci, Anne Catherine Abel, Stefano Pieraccini, Sara Pellegrino, Isabella Rimoldi
Summary: This article investigates the use of a dimeric cyclic cysteine analogue as a constrained unnatural amino acid and a folding inducer in ultra-short peptides. The results demonstrate that both the free dimer amino acid L1 and its peptide derivative L2 can chelate Cu(II). The resulting complexes exhibit catalytic activity in the Michael addition reaction of nitromethane on different types of chalcones, with L1-Cu(II) showing higher reactivity in terms of conversion and L2-Cu(II) achieving an interesting 60% enantiomeric excess on pyridine chalcone.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Crescenzo Coppa, Andrea Bazzoli, Maral Barkhordari, Alessandro Contini
Summary: This study evaluated the performance of accelerated molecular dynamics (aMD) protocols in predicting the secondary structure of eight peptides, including helical, fi-hairpin, and disordered peptides. The results showed that all three combinations of force fields and solvation models performed well on helical peptides. For fi-hairpins, the ff19SB force field combined with both solvation methods showed good performance, with a slight preference for the TIP3P solvation model. The ff19SB/OPC combination exhibited the best performance on intrinsically disordered peptides. However, the ff14SB/TIP3P combination had a strong bias towards helical peptides.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Serena Delbue, Elena Pariani, Silvia Parapini, Cristina Galli, Nicoletta Basilico, Sarah D'Alessandro, Sara Pellegrino, Elena Pini, Samuele Ciceri, Patrizia Ferraboschi, Paride Grisenti
Summary: Lysozyme, a protein widely found in nature, is a part of the innate defense mechanisms in humans, with antimicrobial activity against certain bacteria. It has also shown potential antiviral activity, leading to research on its application in treating SARS-CoV-2 infections.
Article
Multidisciplinary Sciences
David P. Tilly, Jean-Paul Heeb, Simon J. Webb, Jonathan Clayden
Summary: Molecular biology controls complex reaction networks by translating a chemical input into an orthogonal chemical output, but dynamic foldamers have been limited by stereochenical changes that produce spectroscopic signals. In this study, the authors introduce an artificial molecular translation device that converts a chemical input into an unrelated chemical output. This device modulates the reactivity of an imidazole moiety by the presence of chloride ions through the allosteric remote control of imidazole tautomer states.
NATURE COMMUNICATIONS
(2023)
Review
Microbiology
Mickael Guerin, Marc Shawky, Ahed Zedan, Stephane Octave, Berangere Avalle, Irene Maffucci, Severine Padiolleau-Lefevre
Summary: With a high number of cases each year, Lyme borreliosis (LB) is the most common tick-borne illness in the world. The diagnosis of LB is controversial and relies on an indirect approach with low sensitivity. Early and proper detection is crucial for effective treatment and preventing the persistence of the pathogen. This review focuses on improving the current diagnosis and innovative methods for more accurate detection of LB.
Article
Chemistry, Multidisciplinary
David P. Tilly, David T. J. Morris, Jonathan Clayden
Summary: In this study, it was discovered that the ethylene-bridged hydrogen-bonded urea oligomer linear chain has reversible anion coordination and cascade conformational changes. The polarity reversals of hydrogen bonds in the oligomer propagate, resulting in a global switch of hydrogen-bond directionality. This induces a change in emission and excitation wavelengths of a fluorophore at the opposite terminus. Consequently, the molecule acts as a chemical sensor with a relayed remote spectroscopic response to varying anion concentrations. The anion-induced polarity switch provides an artificial communication mechanism for conveying information through oligomeric structures.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
David T. J. Morris, Steven M. Wales, Javier Echavarren, Matej Zabka, Giulia Marsico, John W. Ward, Natalie E. Pridmore, Jonathan Clayden
Summary: Cyclic triureas derived from TACN were synthesized and characterized. Dynamic cyclochirality was observed, with the hydrogen-bonded urea groups exchanging enantiomers through bowl inversion and directionality reversal. Structural modifications were found to affect the enantiomerization barrier, resulting in a planar-chiral, atropisomeric bowl-shaped structure with high stereochemical stability solely from its hydrogen-bonding network.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemical Research Methods
Jean-Paul Heeb, Jonathan Clayden, Martin D. Smith, Roly J. Armstrong
Summary: This article describes three experimental methods, namely kinetic analysis, dynamic HPLC, and variable-temperature NMR, for measuring the rate of racemization in atropisomers. Atropisomers are molecules that exhibit stereochemistry from restricted bond rotation and are highly relevant in catalysis, medicine, and materials science. The methods presented in this article provide techniques for evaluating the configurational stability of atropisomeric molecules and can be performed using standard analytical equipment. The article also discusses the selection of a suitable method for determining racemization rates for new molecular structures with unknown properties.
Article
Chemistry, Organic
Marta Papis, Raffaella Bucci, Alessandro Contini, Maria Luisa Gelmi, Leonardo Lo Presti, Giovanni Poli, Gianluigi Broggini, Camilla Loro
Summary: A phosphine-catalyzed domino assembly of six units of 2-bromomethyl acrylates was developed to synthesize polyalkenyl adducts containing two cyclohexenyl rings. This method involves initial dimerization and subsequent trimerization of the substrate, resulting in the formation of seven carbon-carbon bonds and four stereocenters. The protocol has also been successfully scaled up to gram-scale experiments.
Article
Multidisciplinary Sciences
Ellie Stammers, Chris D. Parsons, Jonathan Clayden, Alastair J. J. Lennox
Summary: In this paper, an electrochemical method is described for the synthesis of biaryls through metal-catalyst-free coupling. The temporary formation and reduction of ureas are utilized to enhance the synthesis yield.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Thomas Binet, Berangere Avalle, Miraine Davila Felipe, Irene Maffucci
Summary: AptaMat, a simple and sensitive algorithm, has been developed for comparing the secondary structures of single-stranded nucleic acids (ssNAs). It outperforms other commonly used metrics in discriminating similar structures and correctly classifying RFAM families during clustering.
Review
Chemistry, Multidisciplinary
David T. J. Morris, Jonathan Clayden
Summary: Biological systems and foldamer chemistry both exploit the propagation of conformational change to communicate information on the molecular scale. Switchable screw-sense preference is a communication mechanism that utilizes dynamic helical foldamers to transmit information. This review discusses the functional requirements for communication devices and describes the use of various stimuli to switch the screw sense. It also explores how conformational switching can control chemical events remote from the source of information.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
David P. Tilly, Matej Zabka, Inigo Vitorica-Yrezabal, Hazel A. Sparkes, Natalie Pridmore, Jonathan Clayden
Summary: This paper investigates the formation mechanism of higher-order structures of ethylene-bridged oligoureas in both crystalline and solution states. The oligoureas self-assemble into supramolecular nanorings or helical chains through hydrogen bonding interactions. The formation of intermolecular hydrogen bonds at the terminus of the oligoureas switches the directionality of the hydrogen bond chain, promoting further assembly. The helices in the crystal state have identical handedness and polarity, and the interactions in solution are consistent with those in the crystals. The switch of hydrogen bond polarity propagates intermolecularly, constituting an example of intermolecular communication within supramolecular polymers.
