Catalyzed ring closure

Despite the unique reactivity of vitamin B12 and its derivatives, B12-dependent enzymes remain underutilized in biocatalysis. In this study, we repurpose the B12-dependent transcription factor CarH to enable non-native radical cyclization reactions. An engineered variant of this enzyme, CarH*, catalyzes the formation γ- and δ-lactams via either redox-neutral or reductive ring closure with marked enhancement of reactivity and selectivity relative to the free B12 cofactor. CarH* also catalyzes an unusual spirocyclization via dearomatization of pendant arenes to produce bicyclic 1,3-diene products instead of 1,4-dienes provided by existing methods...

The synthesis of (±)-angustatin A, a phenanthrene-containing cyclophane that possesses conformational chirality, is reported. Key steps include a Pd-catalyzed Negishi coupling to assemble the necessary terphenyl intermediate, its closure into a 14-membered macrocycle via a catalytic-in-phosphine Wittig olefination, and finally a Pt-catalyzed alkyne hydroarylation, which is able to assemble the phenanthrene unit despite the thermodynamic cost of significantly bending arene A from the ideal plane.

Terpene cyclization, one of the most complex chemical reactions in nature, is generally catalyzed by two classes of terpene cyclases (TCs). Cytochrome P450s that act as unexpected TC-like enzymes are known but are very rare. In this study, we genome-mined a cryptic bacterial terpenoid gene cluster, named ari, from the thermophilic actinomycete strain Amycolatopsis arida. By employing a heterologous production system, we isolated and characterized three highly oxidized eunicellane derived diterpenoids, aridacins A-C (1-3), that possess a 6/7/5-fused tricyclic scaffold...

2,3-dihydrofurans were synthesized from carbonyl-ylides via 1,5-electrocyclization reactions with high yields. Dimethyl diazomalonate was reacted with several β-alkoxy and/or β-phenoxy α,β-unsaturated compounds in the presence of Cu(acac)2 as a catalyst. From the reaction of β-methoxy enone with diazo compound, dioxole, and Cα-H insertion products were also obtained as side products along with 2,3-dihydrofuran derivative. When the unsaturated compound has an ester and a ketone group, only one dihydrofuran derivative was formed, which occurred by the 1,5-ring closure of keto-carbonyl ylide...

The biodegradability of many fluorinated compounds is limited due to the robustness of the C-F bond. Recently, experimental studies suggested the potential involvement of cytochrome P450 enzymes in facilitating aromatic defluorination, raising questions where this can be applied in biocatalysis. Our study offers an in-depth computational examination into the oxidative defluorination process of a drug molecule, mediated by cytochrome P450 Compound I. We explored a large number of potential mechanisms, and identify two competitive low-energy pathways that are initiated with an electrophilic attack on the aromatic ring, and followed by either a 1,2-fluorine shift or a ring-closure to form an epoxide intermediate...

Cyclopropanes are key features in many preclinical, clinical, and commercial drugs, as well as natural products. The most prolific technique for their synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, a highly energetic reagent requiring stringent safety precautions. Discovery of alternative innocuous reagents remains an ongoing challenge. Herein, we report a simple photoredox-catalyzed intermolecular cyclopropanation of unactivated alkenes with active methylene compounds. The reaction proceeds in neutral solvent under air or dioxygen (O2 ) with a photoredox catalyst excited by blue light-emitting diode light and an iodine co-catalyst that is either added as molecular iodine or generated in situ from alkyl iodides...

Herein, a novel route to atropisomeric N -aryl quinolones with low rotational barriers is demonstrated, leveraging a dual photochemical/organocatalytic approach to the required ring closure in up to 94% yield and up to >99% ee. The use of a continuous flow system allows for impurity suppression and enables rapid scale-up to a decagram scale.

Al-containing catalysts, e.g., Al(OTf)3 , show good catalytic performance toward the conversion of cellulose to fructose in methanol solution. Here, we report the catalytic isomerization and alcoholysis mechanisms for the conversion of cellobiose to fructose at the PBE0/6-311++G(d,p), aug-cc-pVTZ theoretical level, combining the relevant experimental verifications of electrospray ionization mass spectrometry (ESI-MS), high-performance liquid chromatography (HPLC), and the attenuated total reflection-infrared (ATR-IR) spectra...

The need for sustainable and environment-friendly materials has led to growing interest in the development of biodegradable polymers based on natural compounds. However, metal-based catalysts used in the polymerization process may cause concerns about the toxicity of the resultant polymers. Therefore, polymers derived from natural compounds and synthesized through the use of green catalysts are highly desirable. Lipase-catalyzed ring-opening polymerization (ROP) of biocompound-based cyclic monomers has emerged as a promising and green strategy for the design and synthesis of such polymers...

Functionalized 4-aryl-4 H -benzo[ d ][1,3]oxazines are synthesized under transition-metal-free conditions using ortho -amide- N -tosylhydrazones. This synthetic method uses readily available N -tosylhydrazones as the diazo compound precursors and involves an intramolecular ring closure reaction mediated by a protic polar additive ( i PrOH). A wide range of functionalized oxazines are obtained by this straightforward method in good to excellent yields. Furthermore, the viability of our strategy is illustrated by the gram-scale elaboration of a bromo-substituted 4 H -benzo[ d ][1,3]oxazine and its post-functionalization by palladium-catalyzed cross-couplings...

Blumeatin, reported herein, bearing two hydroxyl groups at C3' and C5' of ring B, is isolated from the traditional Chinese medicine Blumea balsamifera . But the isolation procedure of blumeatin from plants has limitations of prolonged duration and high cost. A procedure featuring Lewis acid-catalyzed ring closure and chiral resolution via Schiff base intermediates is provided here to prepare optically pure blumeatin and its R -isomer efficiently. Furthermore, the structure revision of putative blumeatin based on a logically synthetic procedure and NMR spectroscopic analysis was conducted...

Ring-closure is a key step in current pyrimidine anabolism and one may wonder whether cyclisation reactions could be promoted in the geochemical context at the origins of life, i.e. with the help of minerals. Various prebiotic minerals were tested in this work, including silica, carbonates, microporous minerals. In particular the role of zinc ions supported on minerals was investigated in view of its presence in the catalytic site of cyclic amidohydrolase enzymes. Based on in situ (TGA: ThermoGravimetric Analysis, ATR-IR: Attenuated Total Reflectance-InfraRed) and ex situ (1H NMR- Nuclear Magnetic Resonance) characterizations, we identified the products of thermal activation of NCA (N-carbamoyl-aspartic acid) in wetting-and-drying scenarios on the surface of minerals...

ConspectusWell-controlled olefin insertion is critical for achieving catalytic and productive bulk and fine-chemical synthesis. Developing efficient and selective methods for meeting diverse insertion demands is extremely noteworthy, as it supports numerous transformations. The challenges are related to improving catalyst performance and selectivity control and uniting previously unreactive substrate pairs to achieve higher molecular structural complexity and utility. Nickel catalysts have received persistent attention in higher substituted olefin synthesis and polymerization, and numerous new strategies have been established to fulfill the ever-changing demands...

Aziridines are compounds with a nitrogen-containing three-membered ring. When it is incorporated into natural products, the reactivity of the strained ring often drives the biological activities of aziridines. Despite its importance, the enzymes and biosynthetic strategies deployed to install this reactive moiety remain understudied. Herein, we report the use of in silico methods to identify enzymes with potential aziridine-installing (aziridinase) functionality. To validate candidates, we reconstitute enzymatic activity in vitro and demonstrate that an iron(IV)-oxo species initiates aziridine ring closure by the C-H bond cleavage...

Experimentally conducted reactions between CO2 and various substrates ( i.e. , ethylenediamine (EDA), ethanolamine (ETA), ethylene glycol (EG), mercaptoethanol (ME), and ethylene dithiol (EDT)) are considered in a computational study. The reactions were previously conducted under harsh conditions utilizing toxic metal catalysts. We computationally utilize Brønsted acidic ionic liquid (IL) [Et2 NH2 ]HSO4 as a catalyst aiming to investigate and propose 'greener' pathways for future experimental studies. Computations show that EDA is the best to fixate CO2 among the tested substrates: the nucleophilic EDA attack on CO2 is calculated to have a very small energy barrier to overcome (TS1EDA, Δ G ‡ = 1...

Terpene cyclases catalyze one of the most powerful transformations with respect to efficiency and selectivity in natural product (bio)synthesis. In such polyene cyclizations, structurally highly complex carbon scaffolds are built by the controlled ring closure of linear polyenes. Thereby, multiple C,C bonds and stereocenters are simultaneously created with high precision. Structural pre-organization of the substrate carbon chain inside the active center of the enzyme is responsible for the product- and stereoselectivity of this cyclization...

INTRODUCTION: New cyclohexenone derivatives candidates were designed to discover their antioxidant and antibacterial activity potentials, respectively. METHODS: Aldehydes with the diverse functional group were prepared from 4-hydroxy benzaldehyde and benzyl bromide and converted to chalcones by reaction with 4-substituted benzophenones and 2-acetyl naphthalene. When chalcone derivatives were subjected to ethyl acetoacetate, it produced new cyclohexenone derivatives through NaOH- catalyzed addition-ring closure reaction...

Understanding the general mechanism of the metal-free and cofactor-free oxidases and oxygenases catalyzed activation of triplet O2 is one of the most challenging questions in the field of enzymatic catalysis. Herein, we have performed Quantum Mechanics/Molecular Mechanics (QM/MM) multiscale simulations to reveal the detailed mechanism of the HOD catalyzed (i.e., 1- H -3-hydroxy-4-oxoquinaldine 2,4-dioxygenase from Arthrobacter nitroguajacolicus Rü61a ) decomposition of N -heteroaromatic compounds. The complete catalytic mechanism includes four steps: (1) proton transfer from 1- H -3-hydroxy-4-oxoquinaldine (QND) substrate to His251 residue coupled with an electron transfer from QND to triplet O2 (i...

Non-heme iron enzymes are versatile catalysts in the biosynthesis of medicinal natural products and have attracted increasing attention as practical catalytic tools in chemical synthesis due to their ability to perform chemically challenging transformations. The Fe(II)/α-ketoglutarate-dependent oxygenase TqaL catalyzes unusual aziridine formation from l-Val via cleavage of the unactivated Cβ -H bond. However, the mechanistic details as well as the synthetic potential of TqaL-catalyzed ring closure remain unclear...

Enantioselective cyclopropanation of α-carbonyl sulfoxonium ylides (SY) has so far been limited to addition/ring closure reactions on electron-poor olefins. Herein, we report the iridium-catalyzed intramolecular cyclopropanation of SY in the presence of a chiral diene in up to 96% yield and 98% enantioselectivity. Moreover, density functional theory calculations suggest that the re face of the olefin preferably attacks an iridium carbene intermediate in an asynchronous concerted step that is independent of the geometry of the olefin...