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1.
Yakugaku Zasshi ; 140(9): 1087-1094, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879240

RESUMO

This review, based on my research work, introduces and summarizes the synthesis and characterization of novel cyclic compounds containing aminobenzenesulfonamide. The review discusses the (1) development of sequential Nicholas and Pauson-Khand reactions for the synthesis of unique polyheterocyclic compounds, (2) production of 2-aminobenzenesulfonamide-containing cyclononyne (ABSACN) as a multifunctional click cycloalkyne agent, and (3) improvement of the intramolecular Pauson-Khand reaction of the nitroarene-enyne substrate for the synthesis of cyclopenta[c]piperidine alkaloids. This research work will facilitate the discovery of sulfonamide or sultam-based functional molecules and pharmaceuticals. Thus, I believe that aminobenzenesulfonamide derivatives are versatile and valuable chemical moieties not only in organic syntheses but also in the pharmaceutical industry. If you are interested in the details of this topic, please refer to the original papers.


Assuntos
Sulfonamidas/síntese química , Ciclização , Cicloparafinas/síntese química , Fenômenos de Química Orgânica , Piperidinas/síntese química , Sulfonamidas/química
2.
Yakugaku Zasshi ; 140(9): 1101-1106, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879242

RESUMO

Organoselenium compounds have attracted significant interest because of their use as important reagents in organic syntheses and potential biological activities, necessitating the development of simple and general synthetic methods. This article reviews our studies to develop of copper-catalyzed C-Se bond formation reactions via cross coupling and C-H activation. A number of unsymmetrical and symmetrical diaryl selenides were synthesized via Se-arylation of diaryl diselenides or selenium powder with triarylbismuthanes under aerobic conditions, achieving moderate to excellent yields. When the reaction of triphenylbismuthane with elemental Se was monitored with gas chromatography, diphenyl diselenide and diphenyl selenide formation was confirmed. Subsequently, 1-pot 2-step reactions were performed under mild conditions to obtain 3-selanyl imidazo[1,2-a]pyridines from triarylbismuthanes and diimidazopyridyl diselenides, which were generated from imidazo[1,2-a]pyridines and Se powder, in good to excellent yields. It should be noted that all three aryl groups in the bismuth and both selanyl groups in the diaryl diselenide generated from the selenium source were transferred to the coupling products. Cu-catalyzed tandem cyclization of 2-(2-iodophenyl)imidazo[1,2-a]pyridines with selenium for the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines is also described herein. The molecular structure of the tetracyclic compound features nearly coplanar rings, and the maximum absorption is red-shifted compared to those of imidazo[1,2-a]pyridine and benzoselenophene.


Assuntos
Carbono/química , Cobre/química , Hidrogênio/química , Compostos Organosselênicos/síntese química , Catálise , Ciclização , Ligação de Hidrogênio , Fenômenos de Química Orgânica
3.
Chimia (Aarau) ; 74(9): 699-703, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32958107

RESUMO

Aldol reactions belong to the most important methods for carbon-carbon bond formation and are also involved in one of the most astonishing biosynthetic processes: the biosynthesis of polyketides governed by an extraordinarily sophisticated enzymatic machinery. In contrast to the typical linear or convergent strategies followed in chemical synthesis, this late-stage catalysis concept allows Nature to assemble intermediates that are diversified into a broad range of scaffolds, which assume various crucial biological functions. To transfer this concept to small-molecule catalysis to access products beyond the natural systems, a stepwise approach to differentiate increasingly complex substrates was followed by investigating arene-forming polyketide cyclizations. An outline of our efforts to develop and apply these concepts are presented herein.


Assuntos
Policetídeos , Catálise , Ciclização , Metabolismo Secundário
4.
Nat Commun ; 11(1): 4170, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820174

RESUMO

Sulfur-sulfur motifs widely occur in vital function and drug design, which yearns for polysulfide construction in an efficient manner. However, it is a great challenge to install desired functional groups on both sides of sulfur-sulfur bonds at liberty. Herein, we designed a mesocyclic bilateral disulfurating reagent for sequential assembly and modular installation of polysulfides. Based on S-O bond dissociation energy imparity (mesocyclic compared to linear imparity is at least 5.34 kcal mol-1 higher), diverse types of functional molecules can be bridged via sulfur-sulfur bonds distinctly. With these stable reagents, excellent reactivities with nucleophiles including C, N and S are comprehensively demonstrated, sequentially installing on both sides of sulfur-sulfur motif with various substituents to afford six species of unsymmetrical polysulfides including di-, tri- and even tetra-sulfides. Life-related molecules, natural products and pharmaceuticals can be successively cross-linked with sulfur-sulfur bond. Remarkably, the cyclization of tri- and tetra-peptides affords 15- and 18-membered cyclic disulfide peptides with this reagent, respectively.


Assuntos
Dissulfetos/química , Indicadores e Reagentes/química , Peptídeos/química , Sulfetos/química , Enxofre/química , Produtos Biológicos/química , Técnicas de Química Sintética/métodos , Ciclização , Indicadores e Reagentes/síntese química , Modelos Químicos , Estrutura Molecular , Oxirredução , Preparações Farmacêuticas/química
5.
PLoS One ; 15(6): e0234901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579565

RESUMO

Lasso peptides are unique in that the tail of the lasso peptide threads through its macrolactam ring. The unusual structure and biological activity of lasso peptides have generated increased interest from the scientific community in recent years. Because of this, many new types of lasso peptides have been discovered. These peptides can be synthesized by microorganisms efficiently, and yet, their chemical assembly is challenging. Herein, we investigated the possibility of high pressure inducing the cyclization of linear precursors of lasso peptides. Unlike other molecules like rotaxanes which mechanically interlock at high pressure, the threaded lasso peptides did not form, even at pressures the high pressure up to 14 000 kbar.


Assuntos
Peptídeos/química , Peptídeos/síntese química , Sequência de Aminoácidos , Ciclização , Dissulfetos/química , Oxirredução , Pressão , Conformação Proteica , Soluções
6.
Sheng Wu Gong Cheng Xue Bao ; 36(5): 920-931, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32567275

RESUMO

The capacity for thermal tolerance is critical for industrial enzyme. In the past decade, great efforts have been made to endow wild-type enzymes with higher catalytic activity or thermostability using gene engineering and protein engineering strategies. In this study, a recently developed SpyTag/SpyCatcher system, mediated by isopeptide bond-ligation, was used to modify a rumen microbiota-derived xylanase XYN11-6 as cyclized and stable enzyme C-XYN11-6. After incubation at 60, 70 or 80 ℃ for 10 min, the residual activities of C-XYN11-6 were 81.53%, 73.98% or 64.41%, which were 1.48, 2.92 or 3.98-fold of linear enzyme L-XYN11-6, respectively. After exposure to 60-90°C for 10 min, the C-XYN11-6 remained as soluble in suspension, while L-XYN11-6 showed severely aggregation. Intrinsic and 8-anilino-1-naphthalenesulfonic acid (ANS)-binding fluorescence analysis revealed that C-XYN11-6 was more capable of maintaining its conformation during heat challenge, compared with L-XYN11-6. Interestingly, molecular cyclization also conferred C-XYN11-6 with improved resilience to 0.1-50 mmol/L Ca²âº or 0.1 mmol/L Cu²âº treatment. In summary, we generated a thermal- and ion-stable cyclized enzyme using SpyTag/SpyCatcher system, which will be of particular interest in engineering of enzymes for industrial application.


Assuntos
Endo-1,4-beta-Xilanases , Estabilidade Enzimática , Microbiologia Industrial , Microbiota , Rúmen , Animais , Ciclização , Endo-1,4-beta-Xilanases/química , Endo-1,4-beta-Xilanases/metabolismo , Microbiologia Industrial/métodos , Engenharia de Proteínas , Rúmen/enzimologia , Rúmen/microbiologia , Temperatura
7.
Biochim Biophys Acta Proteins Proteom ; 1868(9): 140459, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474105

RESUMO

In the biological proteins, aspartic acid (Asp) residues are prone to nonenzymatic isomerization via a succinimide (Suc) intermediate. Asp-residue isomerization causes the aggregation and the insolubilization of proteins, and is considered to be involved in various age-related diseases. Although Suc intermediate was considered to be formed by nucleophilic attack of the main-chain amide nitrogen of N-terminal side adjacent residue to the side-chain carboxyl carbon of Asp residue, previous studies have shown that the nucleophilic attack is more likely to proceed via iminol tautomer when the water molecules act as catalysts. However, the full pathway to Suc-intermediate formation has not been investigated, and the experimental analyses for the Asp-residue isomerization mechanism at atomic and molecular levels, such as the analysis of the transition state geometry, are difficult. In the present study, we computationally explored the full pathways for Suc-intermediate formation from Asp residues. The calculations were performed two types of reactant complexes, and all energy minima and TS geometries were optimized using B3LYP density functional methods. As a result, the SI-intermediate formation was divided into three processes, i.e., iminolization, cyclization, and dehydration processes, and the activation energies were calculated to be 26.1 or 28.4 kcal mol-1. These values reproduce the experimental data. The computational results show that abundant water molecules in living organisms are effective catalysts for the Asp-residue isomerization.


Assuntos
Ácido Aspártico/química , Modelos Químicos , Succinimidas/síntese química , Água/química , Amidas , Catálise , Ciclização , Isomerismo , Modelos Moleculares , Nitrogênio , Proteínas/química
8.
Yakugaku Zasshi ; 140(4): 455-470, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238625

RESUMO

Natural products are useful sources in the search for biochemical probes and drug leads because of their unique biological activities. However, synthetic studies or functional analyses of polycyclic complex natural products or conjugated lipids (e.g., glycolipids) are often hampered because of their synthesis and handling are challenging. On the basis of rational designs, synthetic studies, and chemical modifications, natural products need to be optimized to more potent compounds with improved activities, selectivities and/or physical properties. We have been synthesizing natural products and their derivatives for the elucidation of their biological mechanisms and discovery of drug leads. This review describes three topics for developing functional compounds derived from natural products for prospective involvement in pharmaceutical research: 1) direct construction of the ergot alkaloid scaffold by palladium catalyzed domino cyclization of amino allenes; 2) identification of novel sphingosine kinase inhibitors through a structure-activity relationship study of jaspine B; and 3) design, synthesis and biological evaluation of novel CD1d glycolipid ligands containing modified lipid moieties.


Assuntos
Produtos Biológicos/síntese química , Alcadienos/química , Antígenos CD1d , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Catálise , Fenômenos Químicos , Ciclização , Desenvolvimento de Medicamentos , Alcaloides de Claviceps/química , Glicolipídeos , Ligantes , Paládio/química , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Relação Estrutura-Atividade
9.
Nucleic Acids Res ; 48(9): 5147-5156, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32282905

RESUMO

Cyclization of DNA with sticky ends is commonly used to measure DNA bendability as a function of length and sequence, but how its kinetics depend on the rotational positioning of the sticky ends around the helical axis is less clear. Here, we measured cyclization (looping) and decyclization (unlooping) rates (kloop and kunloop) of DNA with sticky ends over three helical periods (100-130 bp) using single-molecule fluorescence resonance energy transfer (FRET). kloop showed a nontrivial undulation as a function of DNA length whereas kunloop showed a clear oscillation with a period close to the helical turn of DNA (∼10.5 bp). The oscillation of kunloop was almost completely suppressed in the presence of gaps around the sticky ends. We explain these findings by modeling double-helical DNA as a twisted wormlike chain with a finite width, intrinsic curvature, and stacking interaction between the end base pairs. We also discuss technical issues for converting the FRET-based cyclization/decyclization rates to an equilibrium quantity known as the J factor that is widely used to characterize DNA bending mechanics.


Assuntos
DNA/química , Ciclização , Transferência Ressonante de Energia de Fluorescência , Cinética , Modelos Moleculares , Conformação de Ácido Nucleico
10.
Nat Commun ; 11(1): 1575, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221295

RESUMO

Asparaginyl endopeptidases (AEPs) catalyze the key backbone cyclization step during the biosynthesis of plant-derived cyclic peptides. Here, we report the identification of two AEPs from Momordica cochinchinensis and biochemically characterize MCoAEP2 that catalyzes the maturation of trypsin inhibitor cyclotides. Recombinantly produced MCoAEP2 catalyzes the backbone cyclization of a linear cyclotide precursor (MCoTI-II-NAL) with a kcat/Km of 620 mM-1 s-1, making it one of the fastest cyclases reported to date. We show that MCoAEP2 can mediate both the N-terminal excision and C-terminal cyclization of cyclotide precursors in vitro. The rate of cyclization/hydrolysis is primarily influenced by varying pH, which could potentially control the succession of AEP-mediated processing events in vivo. Furthermore, MCoAEP2 efficiently catalyzes the backbone cyclization of an engineered MCoTI-II analog with anti-angiogenic activity. MCoAEP2 provides enhanced synthetic access to structures previously inaccessible by direct chemistry approaches and enables the wider application of trypsin inhibitor cyclotides in biotechnology applications.


Assuntos
Biocatálise , Cisteína Endopeptidases/metabolismo , Inibidores da Tripsina/metabolismo , Sequência de Aminoácidos , Ciclização , Concentração de Íons de Hidrogênio , Cinética , Modelos Moleculares , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo , Proteínas de Plantas/metabolismo , Engenharia de Proteínas , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
11.
Chem Commun (Camb) ; 56(26): 3741-3744, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32124910

RESUMO

Continuous efforts have been invested in the selective modification of proteins. Herein, we first report the construction of sulfonium tethered cyclic peptides via an intramolecular cyclization by an aliphatic halide. This cyclization could enhance the stability and cellular uptake of peptides. Furthermore, the sulfonium center could be recognized by cysteine in the vicinity of the protein-peptide interacting interface and form a peptide-protein conjugate.


Assuntos
Metionina/química , Peptídeos Cíclicos/química , Compostos de Sulfônio/química , Alquilação , Transporte Biológico , Ciclização , Células HeLa , Humanos , Peptídeos Cíclicos/farmacologia
12.
Chem Commun (Camb) ; 56(27): 3903-3906, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32141463

RESUMO

A series of macrocyclic molecules were self-assembled via imine condensation. In order to overcome the insolubility and lability of the amino precursors, amine deprotection and imine condensation are performed in a one-pot manner. Conformation preorganization of the precursors leads to high-yielding self-assembly of the cage products.


Assuntos
Iminas/química , Compostos Macrocíclicos/química , Aminas/química , Ciclização , Conformação Molecular
13.
Org Biomol Chem ; 18(13): 2432-2446, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32163085

RESUMO

This work reports the construction of key building blocks towards the synthesis of cortistatins; a family of steroidal alkaloids. Cortistatin A, being a primary target due to its superior biological properties over other congeners, has been prepared by two different synthetic routes. Synthesis of the precursor to the heavily substituted A-ring starting from d-glucose and construction of the DE-ring junction employing a Hajos-Parrish ketone as a chiral pool have been demonstrated. Efforts are underway to assemble these key fragments and build towards the total synthesis of cortistatin A.


Assuntos
Alcaloides/síntese química , Homosteroides/síntese química , Ciclização , Estereoisomerismo
14.
Org Biomol Chem ; 18(13): 2372-2386, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32196052

RESUMO

Nanographenes are a popular area of research due to their promising properties for electronics. Over the last twenty years there has been a significant increase in interest in the development of contorted nanographenes. While many top-down techniques are employed in the synthesis of these planar nanographenes, the use of alkynes in bottom-up syntheses allows for easy functionalization and the development of contorted nanographenes. The syntheses of contorted nanographenes with a focus on utilizing alkynes is reviewed here.


Assuntos
Alquinos/química , Grafite/química , Nanoestruturas/química , Ciclização , Grafite/síntese química , Conformação Molecular
15.
World J Microbiol Biotechnol ; 36(2): 33, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060755

RESUMO

Microbiota from herbivore rumen is of great interest for mining glycoside hydrolases for lignocellulosic biomass biorefinement. We previously isolated a highly active but poorly thermostable xylanase (LXY) from a rumen fluid fosmid library of Hu sheep, a local high-reproductive species in China. In this study, we used a universal enzyme-engineering strategy called SpyTag/SpyCatcher molecular cyclization to improve LXY stability via isopeptide-bond-mediated ligation. Both linear and cyclized LXY (L- and C-LXY, respectively) shared similar patterns of optimal pH and temperature, pH stability, and kinetic constants (km and Vmax). However, the C-LXY showed enhanced thermostability, ion stability, and resilience to aggregation and freeze-thaw treatment than L-LXY, without compromise of its catalytic efficiency. Circular dichroism and intrinsic and 8-anilino-1-naphthalenesulfonic acid-binding fluorescence analysis indicated that the cyclized enzyme was more capable of maintaining its secondary and tertiary structures than the linear enzyme. Taken together, these results promote the cyclized enzyme for potential applications in the feed, food, paper pulp, and bioenergy industries.


Assuntos
Endo-1,4-beta-Xilanases/química , Endo-1,4-beta-Xilanases/genética , Engenharia de Proteínas/métodos , Rúmen/enzimologia , Animais , Catálise , Dicroísmo Circular , Ciclização , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Ovinos , Termodinâmica
16.
Org Biomol Chem ; 18(10): 1851-1876, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32101232

RESUMO

The growing emphasis on macrocycles in engaging difficult therapeutic targets such as protein-protein interactions and GPCRs via preferential adaptation of bioactive and cell penetrating conformations has provided impetus to the search for de novo macrocyclization strategies that are efficient, chemically robust and amenable to diversity creation. An emerging macrocyclization paradigm based on the C-H activation logic, of particular promise in the macrocyclization of complex peptides, has added a new dimension to this pursuit, enabling efficacious access to macrocycles of various sizes and topologies with high atom and step economy. Significant achievements in macrocyclization methodologies and their applications in the synthesis of bioactive natural products and drug-like molecules, employing strategic variations of C-H activation are captured in this review. It is expected that this timely account will foster interest in newer ways of macrocycle construction among practitioners of organic synthesis and chemical biology to advance the field.


Assuntos
Carbono/química , Hidrogênio/química , Peptídeos Cíclicos/síntese química , Técnicas de Química Sintética/métodos , Ciclização
17.
Anal Bioanal Chem ; 412(7): 1639-1652, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016570

RESUMO

The ratio between reduced and oxidized thiols, mainly glutathione and oxidized glutathione, is one of the biomarkers for the evaluation of oxidative stress. The accurate measurement of thiol concentrations is challenging because reduced thiols are easily oxidized during sample manipulation. Derivatization is commonly used to protect thiols from oxidation. The objective of this work was to systematically compare two cell-permeable derivatizing agents: N-ethyl maleimide (NEM) and (R)-(+)-N-(1-phenylethyl)maleimide (NPEM) in terms of derivatization efficiency, ionization enhancement, side product formation, reaction selectivity for thiols, pH dependence of the reaction, and derivative stability. All thiol measurements and the characterization of side products were performed using a biphenyl reversed phase liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Four thiols, cysteine (CYS), homocysteine, N-acetylcysteine (NAC), and glutathione (GSH), were used for the evaluation. Using 1:10 ratio of thiol:derivatizing agent, complete derivatization was obtained within 30 min for both agents tested with the exception of CYS-NEM, where 97% efficiency was obtained. The more hydrophobic NPEM provided better ionization of the thiols, with enhancement ranging from 2.1x for GSH to 5.7x for CYS in comparison to NEM. NPEM derivatization led to more extensive side reactions, such as double derivatization and ring opening, which hindered the accurate measurement of the thiol concentrations. Both NEM and NPEM also showed poor stability of CYS derivative due to its time-dependent conversion to cyclic cysteine-maleimide derivative. Both reagents also showed significant reactivity with amine-containing metabolites depending on the pH used during derivatization, but overall NEM was found to be more selective towards thiol group than NPEM. Taking into account all evaluation criteria, NEM was selected as a more suitable reagent for the thiol protection and derivatization, but strict control of pH 7.0 is recommended to minimize the side reactions. This work illustrates the importance of the characterization of side products and derivative stability during the evaluation of thiol derivatizing agents and contributes fundamental understanding to improve the accuracy of thiol determinations. The key sources of errors during maleimide derivatization include the derivatization of amine-containing metabolites, poor derivative stability of certain thiols (CYS and NAC), and the side reactions especially if ring opening of the reagent is not minimized. Graphical abstract.


Assuntos
Cromatografia Líquida/métodos , Etilmaleimida/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Compostos de Sulfidrila/química , Ciclização , Concentração de Íons de Hidrogênio
18.
Nature ; 580(7802): 220-226, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32066140

RESUMO

Multicomponent reactions are relied on in both academic and industrial synthetic organic chemistry owing to their step- and atom-economy advantages over traditional synthetic sequences1. Recently, bicyclo[1.1.1]pentane (BCP) motifs have become valuable as pharmaceutical bioisosteres of benzene rings, and in particular 1,3-disubstituted BCP moieties have become widely adopted in medicinal chemistry as para-phenyl ring replacements2. These structures are often generated from [1.1.1]propellane via opening of the internal C-C bond through the addition of either radicals or metal-based nucleophiles3-13. The resulting propellane-addition adducts are then transformed to the requisite polysubstituted BCP compounds via a range of synthetic sequences that traditionally involve multiple chemical steps. Although this approach has been effective so far, a multicomponent reaction that enables single-step access to complex and diverse polysubstituted drug-like BCP products would be more time efficient compared to current stepwise approaches. Here we report a one-step three-component radical coupling of [1.1.1]propellane to afford diverse functionalized bicyclopentanes using various radical precursors and heteroatom nucleophiles via a metallaphotoredox catalysis protocol. This copper-mediated reaction operates on short timescales (five minutes to one hour) across multiple (more than ten) nucleophile classes and can accommodate a diverse array of radical precursors, including those that generate alkyl, α-acyl, trifluoromethyl and sulfonyl radicals. This method has been used to rapidly prepare BCP analogues of known pharmaceuticals, one of which is substantially more metabolically stable than its commercial progenitor.


Assuntos
Técnicas de Química Sintética , Cobre/química , Pentanos/química , Pentanos/síntese química , Preparações Farmacêuticas/química , Preparações Farmacêuticas/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Ciclização , Preparações Farmacêuticas/metabolismo
19.
Chemistry ; 26(20): 4496-4499, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32073167

RESUMO

ß-Lactams are important structural motifs because of their ubiquity in natural products and pharmaceuticals. We report herein a Cu-catalyzed intramolecular oxidative C(sp3 )-H amidation for the synthesis of ß-lactams using tBuOOtBu. This method is based on Kharasch-Sosnovsky amidation and does not require prefunctionalization of C(sp3 )-H bonds or the installation of a directing group, thereby allowing for the straightforward synthesis of ß-lactams. Our intramolecular functionalization protocol can be extended to diverse benzylic C(sp3 )-H bonds and shows excellent functional-group tolerance.


Assuntos
Cobre/química , beta-Lactamas/síntese química , Catálise , Ciclização , Estrutura Molecular , Oxirredução , Estresse Oxidativo , beta-Lactamas/química
20.
Chemistry ; 26(26): 5794-5798, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32084294

RESUMO

Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.


Assuntos
Lactonas/síntese química , Catálise , Ciclização , Cinética , Lactonas/química , Estrutura Molecular
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