Catalyst For Cyclization Research Articles

Biosynthetic Cyclization Catalysts for the Assembly of Peptide and Polyketide Natural Products.

Many biologically active natural products are synthesized by nonribosomal peptide synthetases (NRPSs), polyketide synthases (PKSs) and their hybrids. These megasynthetases contain modules possessing distinct catalytic domains that allow for substrate initiation, chain extension, processing and termination. At the end of a module, a terminal domain, usually a thioesterase (TE), is responsible for catalyzing the release of the NRPS or PKS as a linear or cyclized product. In this review, we address the general cyclization mechanism of the TE domain, including oligomerization and the fungal C-C bond forming Claisen-like cyclases (CLCs). Additionally, we include examples of cyclization catalysts acting within or at the end of a module. Furthermore, condensation-like (CT) domains, terminal reductase (R) domains, reductase-like domains that catalyze Dieckmann condensation (RD), thioesterase-like Dieckmann cyclases, trans-acting TEs from the penicillin binding protein (PBP) enzyme family, product template (PT) domains and others will also be reviewed. The studies summarized here highlight the remarkable diversity of NRPS and PKS cyclization catalysts for the production of biologically relevant, complex cyclic natural products and related compounds.

Use of Imidazo[1,5‐a]pyridin‐3‐ylidene as a Platform for Metal‐Imidazole Cooperative Catalysis: Silver‐Catalyzed Cyclization of Alkyne‐Tethered Carboxylic Acids

AbstractSilver complexes with 5‐(4‐(tert‐butyl)‐1H‐imidazol‐1‐yl)‐imidazo[1,5‐a]pyridin‐3‐ylidene ligands were synthesized as metal‐imidazole acid‐base cooperative catalysts. Single crystal XRD analysis revealed that the silver atom was located in the vicinity of the imidazole ring and that cationic silver complexes formed dimers through coordination between the silver metal and the imidazole pendant. These cationic silver complexes served as catalysts for cyclization of alkyne‐tethered carboxylic acids. NMR experiments indicated that the dimeric cationic silver complex dissociated to a monomer upon protonation of the imidazole moiety, resulting in coordination of an acetonitrile to the silver atom. DFT calculations supported the acid‐base cooperative action of the silver‐imidazole for the efficient alkyne‐carboxylic acid cyclization.magnified image

Effect of Binders on the Physicochemical and Catalytic Properties of Extrudate-Shaped Beta Zeolite Catalysts for Cyclization of Citronellal

Citronellal cyclization was carried out in a continuous mode over H-beta-25 zeolite-based extrudates in a trickle-bed reactor at 35 °C and 10 bar of Ar. The physicochemical properties of zeolitic c...

A new pathway to pyrrolo[1,2-a]quinoxalines via solvent-free one-pot strategy utilizing FeMoSe nanosheets as efficient recyclable synergistic catalyst

FeMoSe nanocatalyst was synthesized using solvothermal approach from readily available precursors, namely Mo(CO)6, FeSO4 and Se, and characterized by spectroscopic and microscopic analyses. The FeMoSe material offered high catalytic activity in the synthesis of pyrrolo[1,2-a]quinoxalines via solvent-free one-pot strategy starting from 2-nitroanilines. Compared to previous works, the significant advantages of our protocols are: (i) solvent-free simple, direct synthesis; (ii) using phenylacetic acids as both Brønsted acid catalysts and reactants; (iii) no requirement of any external oxidants or reductants; and (iv) recyclable heterogeneous catalyst for cyclization. To our best knowledge, synthesis of pyrrolo[1,2-a]quinoxalines using such a synergistic bimetallic system was not previously reported.

Effect of the Composition of a Nonacid n-Alkane Cyclization Catalyst on Its Physicochemical and Catalytic Properties

Effect of the Composition of a Nonacid n-Alkane Cyclization Catalyst on Its Physicochemical and Catalytic Properties

Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis

Acquisition of new catalytic activity is a relatively rare evolutionary event. A striking example appears in the pathway to the antibiotic lankacidin, as a monoamine oxidase (MAO) family member, LkcE, catalyzes both an unusual amide oxidation, and a subsequent intramolecular Mannich reaction to form the polyketide macrocycle. We report evidence here for the molecular basis for this dual activity. The reaction sequence involves several essential active site residues and a conformational change likely comprising an interdomain hinge movement. These features, which have not previously been described in the MAO family, both depend on a unique dimerization mode relative to all structurally characterized members. Taken together, these data add weight to the idea that designing new multifunctional enzymes may require changes in both architecture and catalytic machinery. Encouragingly, however, our data also show LkcE to bind alternative substrates, supporting its potential utility as a general cyclization catalyst in synthetic biology.

Ionic liquid mediated stereoselective synthesis of alanine linked hybrid quinazoline-4(3H)-one derivatives perturbing the malarial reductase activity in folate pathway

Grimmel’s method was optimized as well as modified leading to the cyclization and incorporation of alanine linked sulphonamide in 4-quinazolin-(3H)-ones. Further, the generation of heterocyclic motif at position-3 of 4-quinazolinones was explored by synthesis of imines, which unfortunately led to an isomeric mixture of stereoisomers. The hurdle of diastereomers encountered on the path was eminently rectified by development of new rapid and reproducible methodology involving the use of imidazolium based ionic liquid as solvents as well as catalyst for cyclization as well as synthesis of imines in situ at position-3 leading to procurement of single E-isomer as the target hybrid heterocyclic molecules. The purity and presence of single isomer was also confirmed by HPLC and spectroscopic techniques. Further, the synthesized sulphonamide linked 4-quinazolin-(3H)-ones hybrids were screened for their antimalarial potency rendering potent entities (4b, 4c, 4 l, 4 t and 4u). The active hybrids were progressively screened for enzyme inhibitory efficacy against presumed receptor Pf-DHFR and h-DHFR computationally as well as in vitro, proving their potency as dihydrofolate reductase inhibitors. The ADME properties of these active molecules were also predicted to enhance the knowhow of the oral bioavailability, indicating good bioavailability of the active entities.

The role of Lewis acid–base pair sites in ZnO–ZnCr2O4 catalysts for cyclization via dehydrogenative condensation of crude glycerol and 1,2-propanediamine for the synthesis of 2,6-dimethylpyrazine

DRIFT spectroscopic data revealed the role of surface Lewis acid sites on the synthesis of 2,6-dimethylpyrazine.

Palladium‐catalyzed cyclization of 2‐alkynyl‐N‐ethanoyl anilines to indoles: synthesis, structural, spectroscopic, and mechanistic study

This study reports a facial regio‐selective synthesis of 2‐alkyl‐N‐ethanoyl indoles from substituted‐N‐ethanoyl anilines employing palladium (II) chloride, which acts as a cyclization catalyst. The mechanistic trait of palladium‐based cyclization is also explored by employing density functional theory. In a two‐step mechanism, the palladium, which attaches to the ethylene carbons, promotes the proton transfer and cyclization. The gas‐phase barrier height of the first transition state is 37 kcal/mol, indicating the rate‐determining step of this reaction. Incorporating acetonitrile through the solvation model on density solvation model reduces the barrier height to 31 kcal/mol. In the presence of solvent, the electron‐releasing (–CH3) group has a greater influence on the reduction of the barrier height compared with the electron‐withdrawing group (–Cl). These results further confirm that solvent plays an important role on palladium‐catalyzed proton transfer and cyclization. For unveiling structural, spectroscopic, and photophysical properties, experimental and computational studies are also performed. Thermodynamic analysis discloses that these reactions are exothermic. The highest occupied molecular orbitallowest unoccupied molecular orbital gap (4.9–5.0 eV) confirms that these compounds are more chemically reactive than indole. The calculated UV–Vis spectra by time‐dependent density functional theory exhibit strong peaks at 290, 246, and 232 nm, in good agreement with the experimental results. Moreover, experimental and computed 1H and 13C NMR chemical shifts of the indole derivatives are well correlated. Copyright © 2015 John Wiley & Sons, Ltd.

Direct carbocyclizations of benzoic acids: catalyst-controlled synthesis of cyclic ketones and the development of tandem aHH (acyl Heck-Heck) reactions.

The formation of exo-methylene indanones and indenones from simple ortho-allyl benzoic acid derivatives has been developed. Selective formation of the indanone or indenone products in these reactions is controlled by choice of ancillary ligand. This new process has a low environmental footprint as the products are formed in high yields using low catalyst loadings, while the only stoichiometric chemical waste generated from the reactants in the transformation is acetic acid. The conversion of the active cyclization catalyst into the Hermman-Beller palladacycle was exploited in a one-pot tandem acyl Heck-Heck (aHH) reaction, and utilized in the synthesis of donepezil.

Fe(HSO4 )3 /SiO2: an efficient and heterogeneous catalyst for one-pot synthesis of 2-aryl-chromene-4-ones (flavanones)

Silica ferric hydrogensulphate is an efficient heterogeneous catalyst for cyclisation of 2-hydroxychalcones to their corresponding flavanones (chromanone). This intramolecular oxa-Michael reaction was carried out in high yields in the presence of electron donating and electron withdrawing groups in the chalcone structure. Also, we found that aniline can act as an organic co-catalyst in direct synthesis of flavanones from 2-hydroxyacethophenone and aldehydes in the presence of Fe(HSO4)3/SiO2. Flavanones were prepared in high yields in a new catalytic system with similar substituted effect in the indirect cyclisation method. The catalyst in all the above reactions is reusable without significant decreases in its activity after four times of recycling.

Novel magnetic nanoparticles Fe3O4-immobilized domino Knoevenagel condensation, Michael addition, and cyclization catalyst

Abstract The synthesis, characterization and applications of guanidine supported on magnetic nanoparticles Fe 3 O 4 (MNPs–Guanidine) as a novel magnetically separable base nanocatalyst are described. We have studied the application of this new catalyst for the Knoevenagel condensation reaction of aromatic aldehydes with malononitrile or cyanoacetate in PEG/water = 1:1 at room temperature. Also, the three-component and one-pot synthesis of 2-amino-4 H -chromenes and 2-amino-4 H -benzo[ h ]chromenes by condensing aldehydes, malononitrile and cyclic 1,3-dicarbonyl/α-naphthol, in the presence of catalytic amount of MNPs–Guanidine under same conditions is investigated. The supported catalyst could simply be separated and recovered from the reaction mixture with the assistance of an external magnet and reused several times.

One-Pot Formation of Functionalized Indole and Benzofuran Derivatives Using a Single Bifunctional Ruthenium Catalyst

We report a single bifunctional ruthenium catalyst for cyclization of terminal alkynylaryl amines and -phenols to corresponding indole and benzofuran derivatives in good yields. Key features the ability to cyclize and hydrate terminal alkynes in one step and to deuterate the heteroaromatic compounds formed.

Dehydrative cyclization of serine, threonine, and cysteine residues catalyzed by molybdenum(VI) oxo compounds

Commercially available molybdenum(VI) oxides such as (NH 4) 2MoO 4, (NH 4) 6Mo 7O 24·4H 2O, MoO 2(acac) 2, and MoO 2(TMHD) 2 are highly effective dehydrative cyclization catalysts for the synthesis of a variety of oxazolines. The reaction proceeds with a complete retention of configuration at the β-position. For the dehydrative cyclization of cysteine derivatives, bis(2-ethyl-8-quinolinolato)dioxomolybdenum(VI) shows remarkable catalytic activity and gives thiazolines without a significant loss of stereochemical integrity at the C2-exomethine positions.

2,2-Dimethyl-2,3-dihydropyrano[2,3-a]carbazol-4(11H)-one

The title compound, C17H15NO2, was prepared from 1-hydroxy­carbazole and 3,3-dimethyl­acrylic acid with a mixture of AlCl3 and POCl3 as the cyclization catalyst. Owing to the presence of the –CMe2– group, the mol­ecule is not quite planar. In the crystal structre, strong N—H⋯O hydrogen bonds and weaker C—H⋯π inter­actions occur, and a slipped π–π stacking inter­action [centroid–centroid separation = 3.8425 (8) Å] is also observed.

2,2,10-Trimethyl-2,3-dihydropyrano[2,3-a]carbazol-4(11H)-one

The title compound, C18H17NO2, was prepared from 1-hydr­oxy-8-methyl­carbazole and 3,3-dimethyl­acrylic acid with trifluoro­acetic acid as the cyclization catalyst. Due to the –CMe2– group, the mol­ecule is not quite planar. The packing is dominated by the strong N—H⋯O hydrogen bonds and some weaker C—H⋯O and C—H⋯π inter­actions. π–π Stacking inter­actions [centroid–centroid separation = 3.806 (2) Å] join neighboring mol­ecules into loosely connected inversion dimers.

2,2,9-Trimethyl-2,3-dihydropyrano[2,3-a]carbazol-4-(11H)-one

The title compound, C18H17NO2, was prepared from 1-hydr­oxy-7-methyl­carbazole and 3,3-dimethyl­acrylic acid with trifluoro­acetic acid as the cyclization catalyst. The mol­ecules contain an essentially planar 6-methyl­indole unit. The second aromatic ring is significantly bent away from the plane of this unit, with maximum deviations of 0.171 (1) and 0.185 (1) Å for two of the C atoms. In the crystal structure, there are neither N—H⋯O hydrogen bonds nor π–π stacking between the aromatic sections of neighboring mol­ecules. There is only one weak C—H⋯O hydrogen bond and a number of weak C—H⋯π inter­actions.

Ruthenium‐Catalyzed Intramolecular Cyclization of Hetero‐Functionalized Allylbenzenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

The Iterative Gramicidin S Thioesterase Catalyzes Peptide Ligation and Cyclization

SummaryHere, we present a comprehensive in vitro characterization of the excised iterative, bimodular PCP-TE of the gramicidin S synthetase GrsB, which is able to act both as a ligation and a cyclization catalyst. Using the native pentapeptidyl-thioester substrates, GrsB PCP-TE catalyzes the dimerization and subsequent formation of the decapeptide lactam gramicidin S. Interestingly, the detection of linear decapeptidyl-SNAC as an enzyme-dependent intermediate supports the iterative mechanism in vivo, in which two pentapeptides, one bound as an ester to the active site serine of the TE domain and the second bound as a thioester to the adjacent pan-PCP, are ligated to a decapeptidyl-pan-PCP that subsequently transferred to the adjacent TE domain and cyclized. Moreover, GrsB PCP-TE can handle different substrates length, leading not only to dimerization, but also to trimerization and the formation of different ring sizes.

Ruthenium-catalyzed intramolecular cyclization of hetero-functionalized allylbenzenes

Intramolecular addition of heterofunctionalities to C C double bonds without β-hydride elimination was investigated and catalyzed by ruthenium complexes. The combination of RuCl 3 · nH 2O (10 mol%) and 3 equiv. of AgOTf acted as a catalyst for cyclization of 2-allylphenol ( 1a) to 2,3-dihydro-2-methylbenzofuran ( 2a) in good yield in the presence of Cu(OTf) 2 as a co-catalyst and PPh 3 as a ligand. This catalyst system also catalyzed the cyclization of 2-allylbenzoic acid to lactone in 91% yield. Then, a new catalyst system (RuCp ∗Cl 2) 2 (1.0 mol%)/4AgOTf/4PPh 3, was found to be more active even in the absence of Cu(OTf) 2. Furthermore, this catalysis was applied to asymmetric reaction of 2-allylphenol ( 1a). When using TolBINAP as a ligand, over 60% e.e. was achieved.