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The review considers the mechanism of intramolecular cyclization (intramolecular Diels–Alder reaction) of quaternary ammonium salts simultaneously containing β,γ-unsaturated and various enyne fragments. [ABSTRACT FROM AUTHOR]

The base-catalyzed intramolecular cyclization of (dimethyl)- and (diethyl)-(3-phenylprop-2-enyl)(1-phenylhex-5-en-1-yn-3-yl)ammonium and N-(3-phenylprop-2-enyl)-N-(3-phenylprop-2-ynyl)-piperidinium and -morpholinium bromides was used to synthesize 1-allyl-N,N-diethyl-4-phenyl-1,3,3a,4-tetrahydrobenzo[f]isoindol-2-ium, 1-allyl-N,N-dimethyl-4-phenyl-1,3,3a,4-tetrahydrobenzo[f]isoindol-2-ium, 1-allyl-4-phenyl-1,3,3a,4-tetrahydrospiro(benzo[f]isoindole-2,1'-piperidin)-1'-ium, and 1-allyl-4-phenyl-1,3,3a,4-tetrahydrospiro(benzo[f]isoindole-2,4'-morpholin)-4'-ium bromides in high yields. Cyclization was accompanied by side reactions (8−10%). [ABSTRACT FROM AUTHOR]

Sesterterpenoids are a rare terpene class harboring untapped chemodiversity and bioactivities. Their structural diversity originates primarily from the scaffold-generating sesterterpene synthases (STSs). In fungi, all six known STSs are bifunctional, containing C-terminal trans-prenyltransferase (PT) and N-terminal terpene synthase (TPS) domains. In plants, two colocalized PT and TPS gene pairs from Arabidopsis thaliana were recently reported to synthesize sesterterpenes. However, the landscape of PT and TPS genes in plant genomes is unclear. Here, using a customized algorithm for systematically searching plant genomes, we reveal a suite of physically colocalized pairs of PT and TPS genes for the biosynthesis of a large sesterterpene repertoire in the wider Brassicaceae. Transient expression of seven TPSs from A. thaliana, Capsella rubella, and Brassica oleracea in Nicotiana benthamiana yielded fungal-type sesterterpenes with tri-, tetra-, and pentacyclic scaffolds, and notably (-)-ent-quiannulatene, an enantiomer of the fungal metabolite (+)-quiannulatene. Protein and structural modeling analysis identified an amino acid site implicated in structural diversification. Mutation of this site in one STS (AtTPS19) resulted in premature termination of carbocation intermediates and accumulation of bi-, tri-, and tetracyclic sesterterpenes, revealing the cyclization path for the pentacyclic sesterterpene (-)-retigeranin B. These structural and mechanistic insights, together with phylogenetic analysis, suggest convergent evolution of plant and fungal STSs, and also indicate that the colocalized PT-TPS gene pairs in the Brassicaceae may have originated from a common ancestral gene pair present before speciation. Our findings further provide opportunities for rapid discovery and production of sesterterpenes through metabolic and protein engineering.

Cyclization reaction of poly(acrylonitrile-co-2-acrylamido-2-methylpropane sulfonic acid) [P(AN-co-AMPS)] copolymer during thermal oxidative stabilization (TOS) process was investigated by FTIR and two dimensional (2D) correlation analysis technique. The results showed the mechanism of cyclization reaction at different temperatures were varying. At 200 °C, the cyclization reactions generated by autocatalytic cyclization mechanism. While at higher temperatures, the cyclization reactions took place through ionic cyclization mechanism and free radical cyclization mechanism. The AMPS comonomer could reduce the heat release of cyclization reactions and improve the stability at 200 and 230 °C. At higher temperatures, the cyclization reactions were facilitated rapidly. However, the oxidation and degradation reactions were also intense, which will cause the molecular chain to break and defects in the final carbon fibers (CFs). This research has theoretical guiding significance for the optimization of heat treatment conditions for PAN copolymers used as CFs.

Sesquiterpenes comprise a diverse group of natural products with a wide range of applications in cosmetics, food, medicine, agriculture, and biofuels. Heterologous biosynthesis is increasingly employed for sesquiterpene production, aiming to overcome the limitations associated with chemical synthesis and natural extraction. Sesquiterpene synthases (STSs) play a crucial role in the heterologous biosynthesis of sesquiterpene. Under the catalysis of STSs, over 300 skeletons are produced through various cyclization processes (C1-C10 closure, C1-C11 closure, C1-C6 closure, and C1-C7 closure), which are responsible for the diversity of sesquiterpenes. According to the cyclization types, we gave an overview of advances in understanding the mechanism of STSs cyclization from the aspects of protein crystal structures and site-directed mutagenesis. We also summarized the applications of engineering STSs in the heterologous biosynthesis of sesquiterpene. Finally, the bottlenecks and potential research directions related to the STSs cyclization mechanism and application of modified STSs were presented.

Abstract Exploiting new comonomers is still required for high performance polyacrylonitrile (PAN) based carbon fiber. In this paper, we have proposed an efficient methodology, combining of theoretical calculation and experimental verification, to develop new comonomer for polyacrylonitrile (PAN)-based carbon fiber. The cyclization energy barriers of PAN copolymers, including comonomers of α-nitryl acrylic acid (IA-NO 2), α-amino acrylic acid (IA-NH 2), acrylamide (AAM), itaconic acid (IA), and ethylenesulfonic acid (ESA), have been calculated based on the autocatalytic cyclization mechanism using density functional theory (DFT) at B3LYP/6-31 + G (d, p) level. The theoretical calculation indicated that ionic cyclization of nitrile group was more easily initiated by ESA than other comonomers. Correspondingly, the PAN copolymers including comonomers of ESA and IA have been prepared and studied on their properties. The experimental results further demonstrated the P(AN-co-ESA) copolymer had better thermal properties such as smaller cyclization energy, slower heat release rate, and higher char yielding. Therefore, this theoretical calculation combined with experimental verification methodology is a powerful tool for exploiting new comonomer for PAN-based carbon fiber. Graphical abstract Image 1 Highlights • The cyclization energy barriers of selective comonomers were calculated via DFT. • The nitrile group is more easily initiated by ESA than the others by calculation. • The new comonomer of ESA containing sulfonic group has better thermal properties. • Combined theory and experiment are a useful methodology to exploit new comonomers. [ABSTRACT FROM AUTHOR]

[Display omitted] Fusicoccane (FC)-type diterpenoids are a sub-group of diterpenoids featuring a unique 5 – 8 – 5 tricyclic skeleton, which distribute widely in nature and possess a variety of biological activities. Biosynthesis of FC-type diterpenoids starts with the cyclization of an achiral geranylgeranyl diphosphate to 5 – 8 – 5 tricyclic hydrocarbon skeletons with distinct stereochemistry and various unsaturation patterns by FC-type diterpene synthases (DTSs). Subsequent modifications of hydrocarbons including oxidation, reduction, acylation, methylation and glycosylation give rise to structurally diverse and biologically functional FC-type diterpenoids. Recently, outstanding progress in biosynthesis of FC-type diterpenoids has been achieved through numerous interdisciplinary studies including genome mining, structural biology, and computational chemistry. In this review, we summarize the recent progress in biosynthesis of FC-type diterpenoids, with a special emphasis lying on the cyclization mechanisms of FC-type DTSs. Post-modifications of hydrocarbons to biologically functional FC-type diterpenoids are also covered. [ABSTRACT FROM AUTHOR]

This study details the characterization of a novel and an unexpected cyclization reduction product of Calophyllolide (I), by using sodium borohydride. The structure of the derivative (II) was established as 6,10,11-tetramethyl-4-phenyl-6, 10-dihydro-2H-dipyrano [2, 3-f: 2′, 3′-h] chromen-2-one by 2D NMR experiments such as 1H-1H gCOSY, gHSQC, gHMBC, and LC-MS/MS along with 1H and 13C NMR spectra. A reversed-phase HPLC method and a chiral HPLC method were developed to evaluate the purity and chirality. A reaction mechanism for II was proposed. The synthesized compound was showing significant antimicrobial activity than the parent compound (I) when tested against various pathogenic bacteria and fungus. [ABSTRACT FROM PUBLISHER]

[Display omitted] • First heterologous expression of chimeric STS A8411 in Aspergillus oryzae. • The absolute configuration of hirsutene was determined by x-ray diffraction. • The Biosynthetic mechanism of hirsutene was elucidated by isotope labeling experiment. The high efficiency and elegance of terpene synthases is fascinating in constructing the molecular skeleton of complicated terpenoids with multiple chiral centers. Although the rapid development of sequencing technology has led to the discovery of an increasing number of terpene synthases, the cyclization mechanisms of some terpene synthases remains elusive. Here, we report that a chimeric sesquiterpene synthase from Steccherinum ochraceum is responsible for the biosynthesis of (+)-hirsutene, a linear triquinane sesquiterpene. Structural validation, and isotope labeling experiments demonstrate that the biosynthesis of (+)-hirsutene employs an unusual cyclization mode, involving three different cyclization processes (C1-C11, C2-C9, C3-C6), one intramolecular 1,2-hydride shift (C9-C10) and three successive 1,2-alkyl shifts to construct the 5–5–5 fused ring skeleton of (+)-hirsutene. [ABSTRACT FROM AUTHOR]

Thermal properties of acrylonitrile (AN)-acrylamide (AM) copolymers for carbon fibers were studied by DSC and in situ FTIR techniques in nitrogen (N) and air flows. The cyclization mechanism and stabilization behavior of polyacrylonitrile (PAN) were discussed. In N flow, it was found that AM had the ability to initiate and accelerate cyclization process, which was confirmed by the fact that the initiation of nitriles shifted to a lower temperature. Compared to AN homopolymer, the initiation temperature of cyclization was ahead 32 K by introducing 3.59 mol% AM into the copolymer. The exothermic reaction was relaxed due to the presence of two separated exothermic peaks. Accompanied by DSC, in situ FTIR and calculation of activation energy, the two peaks were proved to be caused by ionic cyclization and free radical cyclization, respectively, and the corresponding cyclization mechanism was proposed. With increasing in AM content, the ionic cyclization tends to be dominant and the total heat liberated first increases and then decreases. For AN homopolymer, the activation energy of cyclization is 179 kJ/mol. For AN-AM copolymer (containing 3.59 mol% AM), the activation energy of ionic cyclization is 96 kJ/mol and that of free radical cyclization is 338 kJ/mol. In air flow, similar cyclization routes occur and the difference is the contribution of oxidation. The oxygen in environment has no remarkable effect on cyclization of AN homopolymer but retards the cyclization of AN-AM copolymers. For AN-AM copolymer with 3.59 mol% AM, the cyclization temperature is postponed 10°C in air. [ABSTRACT FROM AUTHOR]

Terpenes are the largest group of natural products and contain the widest assortment of structural types. Terpene cyclization is also the most complex reaction found in nature. For a long time, terpenoids with diverse structures have attracted natural product chemists to explore their biosynthesis mechanism. Such a large number of terpene skeletons are catalyzed by enzymes called terpene synthase. Sesquiterpene synthase is a kind of terpene synthase, which can catalyze the cyclization of linear precursor farnesyl pyrophosphate(FPP) to sesquiterpene skeletons. Sesquiterpene synthase cyclize a single precursor FPP into many sesquiterpene skeletons. With the continuous discovery of sesquiterpene synthase, the cyclization mechanism of sesquiterpene synthase has been studied deeply. In recent years, with the development and improvement of isotope labeling of substrate FPP and structural analysis of sesquiterpene synthase, the structure and cyclization mechanism of sesquiterpene synthase have been studied more systematically and accurately. In this review, we reviewed the progress of the research methods on the mechanism of sesquiterpene cyclization by substrate isotope labeling and protein structure, as well as the summary and prospect of sesquiterpene synthase research.

• A series of general theoretical studies were performed on the cyclization-degradation of poly(dimethylsiloxanes) in vacuum at the atomic-molecular level using DFT method. It attempts to understand clearly for the thermo degradation mechanism in vacuum, and to make clear the relationship between the geometries of transition states and degradation activity. A DFT investigation was performed on the cyclization mechanism during the process of thermal degradation in vacuum for trimethylsilyl-terminated polydimethylsiloxane, methylsiloxane-α,ω-diol and methylsiloxane-1-ol. The formation of an intramolecular, four-centre cyclic transition state results from the flexibility of a main chain and the ability to rearrange siloxane bonds. The energy barrier of the reaction depends mostly on the four-centre cyclic structure, independent of molecular weight, the position of nucleophilic attacking, and products. The replacement of trimethylsilyl by hydroxyl leads to a great decrease of activation energy of degradation reaction, because the energy barrier of the Si-O bond interchange is much higher than that of hydrogen abstraction. The large cyclosiloxane tend to higher degree of cyclization degradation than linear siloxane with the same number Si atoms. From energetic viewpoint, cyclosiloxane products of various sizes have almost equal chance to form. Due to the continuous degradation of large ring, the D 3 accounts for the predominating proportion, and steadily decreasing amounts of D 4 and D 5. Geometries of transition states for the cyclization-degradation of poly(dimethylsiloxane) Image, graphical abstract [ABSTRACT FROM AUTHOR]

Class I terpene synthase (TPS) generates bioactive terpenoids with diverse backbones. Sesterterpene synthase (sester-TPS, C25), a branch of class I TPSs, was recently identified in Brassicaceae. However, the catalytic mechanisms of sester-TPSs are not fully understood. Here, we first identified three nonclustered functional sester-TPSs (AtTPS06, AtTPS22, and AtTPS29) in Arabidopsis thaliana . AtTPS06 utilizes a type-B cyclization mechanism, whereas most other sester-TPSs produce various sesterterpene backbones via a type-A cyclization mechanism. We then determined the crystal structure of the AtTPS18-FSPP complex to explore the cyclization mechanism of plant sester-TPSs. We used structural comparisons and site-directed mutagenesis to further elucidate the mechanism: (1) mainly due to the outward shift of helix G, plant sester-TPSs have a larger catalytic pocket than do mono-, sesqui-, and di-TPSs to accommodate GFPP; (2) type-A sester-TPSs have more aromatic residues (five or six) in their catalytic pocket than classic TPSs (two or three), which also determines whether the type-A or type-B cyclization mechanism is active; and (3) the other residues responsible for product fidelity are determined by interconversion of AtTPS18 and its close homologs. Altogether, this study improves our understanding of the catalytic mechanism of plant sester-TPS, which ultimately enables the rational engineering of sesterterpenoids for future applications., (© 2020 The Author(s).)

• We systematically studied the effects of PAN sequence distribution on its stabilization. • New cyclization initiation mechanisms on the role of itaconic acid were proposed. • Future optimization for making carbon fibers may focus on PAN sequence structures. Poly(acrylonitrile-co-itaconic acid) (PAI) is the most widely used precursor for making high performance carbon fiber. In this study, we synthesized PAI with various contents of itaconic acid (IA) in the range of 0 to 22 mol%. The addition of IA not only changes acrylonitrile (AN) segment length distribution, but also initiate AN cyclization at a lower temperature. The effects of PAI sequence distribution and initiation mechanisms on PAN cyclization were systematically studied by differential scanning calorimetry, nuclear magnetic resonance, Fourier transform infrared spectroscopy and thermogravimetry. These results show how the AN sequence length and the carboxyl groups in IA affect the cyclization reaction, the formed ladder structures, and carbon yields. [ABSTRACT FROM AUTHOR]