Control of the stereochemistry of C14 hydroxyl during the total synthesis of withanolide E and physachenolide C

The stereochemical outcome of the epoxidation of Δ_14–15 cholestanes with mCPBA is controlled by the steric bulk of a C17 substituent. When the C17 is in the β configuration, the epoxide is formed in the α face, whereas if the C17 is trigonal (flat) or the substituent is in the α configuration, the epoxide is formed in the β face. The presence of a hydroxyl substituent at C20 does not influence the stereochemical outcome of the epoxidation.

The epoxide configuration in oxidation of C14–C15 alkenes is determined by the configuration of the C17 substituent.     

Branched EHNBR and its properties with enhanced low-temperature performance and oil resistance

Epoxide nitrile butadiene rubber (ENBR) was prepared via in situ epoxidation from nitrile butadiene rubber (NBR) with acetic acid and hydrogen peroxide. ENBR had been selectively hydrogenated in the presence of a homogeneous Wilkinson catalyst. The hydrogenated epoxide nitrile butadiene rubber (EHNBR) and ENBR were characterized by infra-red and proton nuclear magnetic resonance. No change was noted in the epoxy content of the polymer after the reaction. The catalyst is highly selective in reducing carbon–carbon double bonds in the presence of epoxy groups. DSC analysis reveals the T_g of ENBR varied linearly with molar epoxide content and the T_g value increased by 0.82 °C per mol%. It also found that the introduction of epoxy groups can effectively reduce the extent of crystallization by impairing the regularity of the molecular chain, but crystalline structure was difficult to completely eliminate. Therefore, anhydrides were selected as ring-opening reagents to react with epoxy groups in EHNBR. The products, branched EHNBR, were characterized by infra-red and proton nuclear magnetic resonance. The conversion rate of the epoxide group was calculated by ¹H NMR. The glass transition temperature of EHNBR-g-heptyl group was −34.1 °C, and its DSC curve demonstrated no crystal structure. The coefficient of cold resistance under compression of EHNBR grafted propyl ester was 0.36, which represented a superior low-temperature performance. Furthermore, residual epoxy groups and ester groups extremely enhanced the oil resistance of HNBR.

Epoxide nitrile butadiene rubber (ENBR) was prepared via in situ epoxidation from nitrile butadiene rubber (NBR) with acetic acid and hydrogen peroxide.     

A molecular electron density theory study of the mechanism,chemo- and stereoselectivity of the epoxidation reaction of R-carvone with peracetic acid

The epoxidation reaction of R-carvone 8 with peracetic acid 9 has been studied within the molecular electron density theory at the B3LYP/6-311(d,p) computational level. The chemo- and stereoisomeric reaction paths involving the two C–C double bonds of R-carvone 8 have been studied. DFT calculations account for the high chemoselectivity involving the C–C double bond of the isopropenyl group and the low diastereoselectivity, in complete agreement with the experimental outcomes. The Baeyer–Villiger reaction involving the carbonyl group of R-carvone 8 has also been analysed. A bonding evolution theory analysis of the epoxidation reaction shows the complexity of the bonding changes taking place along this reaction. Formation of the oxirane ring takes place asynchronously at the end of the reaction by attack of anionic oxygen on the two carbons of the isopropenyl C–C double bond.

The epoxidation reaction of R-carvone 8 with peracetic acid 9 has been studied within the molecular electron density theory at the B3LYP/6-311(d,p) computational level.     

Light-driven selective aerobic oxidation of (iso)quinoliniums and related heterocycles

Selective C1–H/C4–H carbonylation of N-methylene iminium salts, catalyzed by visible-light photoredox and oxygen in the air, has been reported. A ruthenium complex acts as a chemical switch to conduct two different reaction pathways and to afford two different kinds of products. In the absence of the ruthenium complex, the Csp²–H bonds adjacent to the nitrogen atoms are oxidized to α-lactams by the N-methyleneiminium substrates themselves as photosensitizers. In the presence of the ruthenium complex, the oxidation reaction site of quinoliniums is switched to the C4 region, resulting in the formation of 4-quinolones. The use of two transformations directly introduces oxygen into the nitrogen heterocyclic skeletons under an air atmosphere.

The selective C1–H/C4–H carbonylation of N-methyleneiminium salts catalyzed by visible-light photoredox reactions and oxygen in the air has been reported.     

Total synthesis of Palmarumycin BGs,C1 and Guignardin E

The first total synthesis of Palmarumycin BG1–3, BG5–6, C₁ and Guignardin E (1–7) were achieved by the same intermediate Palmarumycin C₂ through a N-benzyl cinchoninium chloride-catalyzed epoxidation, an organoselenium-mediated reduction, and a cerium(iii) chloride hydrate-promoted regioselective ring-opening and elimination of cyclic α,β-epoxy ketone as the key steps via6–7 step routes using 1,8-dihydroxynaphthalene (DHN) and 5-methoxytetralone as the starting materials in overall yields of 1.0–17.4%, respectively. Their structures and absolute configurations were characterized and determined by ¹H, ¹³C NMR, IR, HR-ESI-MS and X-ray diffraction data. These compounds displayed significant inhibition activities against HCT116, U87-MG, HepG2, BGC823 and PC9 cell lines.

The first total syntheses of Palmarumycin BG1–3, BG5–6, C₁ and Guignardin E were achieved. These compounds displayed significant inhibition activities against HCT116, U87-MG, HepG2, BGC823 and PC9 cell lines.     

Studies on asymmetric total synthesis of (−)-β-hydrastine via a chiral epoxide ring-opening cascade cyclization strategy

Herein, facile and enantioselective approaches to synthesize the core phthalide tetrahydroisoquinoline scaffold of (−)-β-hydrastine via both a CF₃COOH-catalyzed (86% ee) and KHMDS-catalyzed (78% ee) epoxide ring-opening/transesterification cascade cyclization from chiral epoxide under very mild conditions are described. The key elements include a highly enantioselective epoxidation using the Shi ketone catalyst and an intramolecular CF₃COOH-catalyzed cascade cyclization in one pot, and a late-stage C-3′ epimerization under MeOK/MeOH conditions as the key steps to achieve the first total synthesis of (−)-β-hydrastine (up to 81% ee).

Herein, both CF₃COOH-catalyzed (86% ee) and KHMDS-catalyzed (78% ee) chiral epoxide ring-opening cascade cyclization to facile and enantioselective synthesis of the core phthalide tetrahydroisoquinoline scaffold of (−)-β-hydrastine are described.     

Phase transition behavior and deformation mechanism of polytetrafluoroethylene under stretching

The deformation mechanism and phase transition behavior of polytetrafluoroethylene (PTFE) under stretching conditions (25, 50, 100 °C) were investigated by using differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), and X-ray diffraction (XRD). Compared to the unstretched PTFE samples, stretching at all temperatures results in a reduced phase transition temperature (IV–I and II–IV). Above a critical strain ε_H,c (∼0.6), the decrease of phase transition temperature becomes more significant with the increasing strain. At higher stretching temperature, the value of the ε_H,c becomes smaller. By separating the recoverable (ε_H,r) and irreversible (ε_H,i) deformation, a similar ε_H,c (∼0.6) is found, beyond which the recoverable part remains basically unchanged while the unrecoverable part increases sharply. It is considered that as the strain reaches 0.6, both the untwisting of molecular chain and destroy of the crystal structure could occur, which leads to the increased plastic deformation of the system. Upon the strain is beyond 0.9, the degree of chain untwisting reaches the maximum, and a stable oriented fiber network structure forms, showing the phenomenon of elasticity enhancement. The deformation mechanism of PTFE changes from lamella slip at small strain to stretching induced formation of stable fibrils as evidenced by SEM and SAXS.

The deformation mechanism and phase transition behavior of polytetrafluoroethylene (PTFE) under stretching conditions (25, 50, 100 °C) were investigated by using differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), and X-ray diffraction (XRD).     

Temperature independence of piezoelectric properties for high-performance BiFeO3–BaTiO3 lead-free piezoelectric ceramics up to 300 °C

The temperature-dependence behaviors of ferroelectric, piezoelectric, k_p and electrical-field-induced strain were carefully evaluated for high-performance BiFeO₃–0.3BaTiO₃ (BF–0.3BT) ceramics. There results indicate, combined with Rayleigh analysis and temperature-dependence XRD and PFM, that the increase of strain and large signal with increasing the temperature from room temperature to 180 °C is related to the joint effect of intrinsic contribution (lattice expansion) and extrinsic contribution (domain switching). With further increasing the temperature to 300 °C, the large signal d₃₃ and electrical-field-induced strain mildly decrease because of the increase of conductivity for BF–0.3BT ceramics. However, different from strain and large signal the small signal d₃₃(E₀) and k_p exhibit excellent temperature stability behavior as the temperature increases from room temperature to 300 °C.

The temperature-dependence behaviors of ferroelectric, piezoelectric, k_p and electrical-field-induced strain were carefully evaluated for high-performance BiFeO₃–0.3BaTiO₃ (BF–0.3BT) ceramics.     

Isolation of 5′-O-sulfamyladenosine and related 3′-O-β-glucosylated adenosines from the nucleocidin producer Streptomyces calvus

The isolation of three adenosine based metabolites 6–8 from Streptomyces calvus is reported. The metabolites are structurally related to the fluorine containing antibiotic nucleocidin 1 and two recently identified glycosylated fluoroadenosines 2 and 3, however in this case the three metabolites do not contain a fluorine, suggesting that the biosynthetic enzymes to the fluorometabolites also process their non-fluorinated counterparts.

The isolation of three adenosine based metabolites 6–8 from Streptomyces calvus is reported.     

Penicacids H–J,three new mycophenolic acid derivatives from the marine-derived fungus Rhizopus oryzae

Chemical investigation of secondary metabolites in crude methanol extract of a solid rice medium of a marine-derived fungus, Rhizopus oryzae, has enriched the metabolic profile of this genus by affording three mycophenolic acid derivatives recognized as new fungal metabolites trivially named as penicacids H–J (1–3), along with two known naphtho-γ-pyrone dimers, asperpyrone A (4) and dianhydroaurasperone C (5). Structure elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses together with comparing coupling constant and optical rotation values with those reported for related congeners in literature. All isolated compounds were assessed for their antibacterial activity against four different bacterial microorganisms and they revealed moderate to weak activities with minimum inhibitory concentration (MIC) values ranging from 62.5 to 250 μg mL⁻¹.

Penicacids H–J (1–3), three new natural MPA derivatives, were purified from a marine-derived fungus, Rhizopus oryzae, together with two known naphtho-γ-pyrone dimers, asperpyrone A (4) and dianhydroaurasperone C (5).     

Cytotoxic alkaloids from the marine shellfish-associated fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy

Eight different culture media were used to culture shellfish Panopea abbreviate associated fungus Aspergillus sp. XBB-4. In a glucose-peptone-yeast (GPY) culture medium supplied with amino acids, this fungus can produce chemodiversity metabolites. Four new alkaloids including three β-carboline alkaloids, aspercarbolines A–C (1–3) and one piperazinedione, asperdione A (13) along with nine known compounds were isolated. The structures were elucidated mainly based on the NMR, MS, ECD and X-ray single-crystal diffraction data. The possible biosynthetic pathways of aspercarbolines A–C (1–3) were proposed. All compounds (1–13) were evaluated for their cytotoxicity against six cancer cell lines, including human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and SUNE1, and human hepatocellular carcinoma cell lines hepG2 and QGY7701.

Cytotoxic alkaloids from marine fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy.     

Total synthesis,structure revision and cytotoxic activity of Sch 53825 and its derivatives

The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B₆ was improved using the same raw material with 6 steps and 32% overall yield. Also, three new analogues with two chlorine atoms were synthesized. Their structures were characterized by ¹H, ¹³C NMR, HR-ESI-MS and X-ray diffraction data. The structure of natural Sch 53825 was revised as an epimer of compound 1 with the anti-hydroxy epoxide at C-4. Their cytotoxic activities against several tumor cell lines (HCT116, U251, BGC823, Huh-7 and PC9) showed that compound 11 exhibited excellent cytotoxicity against above mentioned cancer cell lines with IC₅₀ < 0.5 μM.

The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps.     

Anion influences on reactivity and NMR spectroscopic features of NHC precursors

A series of 16 benzimidazolium salts of the type ⁱPr₂-bimyH⁺X⁻ with various anions X were synthesized and characterized by various spectroscopic and spectrometric methods. Significant anion and solvent effects on the chemical shifts of the C2–H protons were found, which allows for a ranking of the anions in terms of their hydrogen-bond acceptor properties. Stronger acceptors could increase the acidity of their respective salts leading to a faster H/D exchange. Similar but less pronounced anion influences were detected for the ¹³C_C2 NMR resonances, while ¹J_C2–H coupling constants appear to be anion and solvent independent.

The influences of 16 different counteranions on hydrogen-bondings, C–H acidities and ¹J_C2–H coupling constants of azolium salts have been studied.     

Hyperelatosides A–E,biphenyl ether glycosides from Hypericum elatoides,with neurotrophic activity

Five new biphenyl ether glycosides, hyperelatosides A–E (1–5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7–15), were isolated from the aerial parts of Hypericum elatoides. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed. Except for 3, the new phenolic metabolites exhibited significant neurotrophic activities to enhance nerve growth factor-induced neurite outgrowth in PC12 cells. In addition, the anti-neuroinflammatory and antioxidant activities of compounds 1–15 were preliminarily evaluated in vitro.

Five new biphenyl ether glycosides, hyperelatosides A–E, one new benzoate glycoside, hyperelatoside F, were isolated from Hypericum elatoides. Hyperelatosides A, B, and D–F significantly enhanced NGF-induced neurite outgrowth in PC12 cells.     

Cobalt-catalyzed C(sp3)–H/C(sp2)–H oxidative coupling between alkanes and benzamides

A direct cobalt-catalyzed oxidative coupling between C(sp²)–H in unactivated benzamides and C(sp³)–H in simple alkanes, ethers and toluene derivatives was explored. This protocol achieves direct C–C formation without using alkyl or aryl halide surrogates and exhibits high practicality with ample substrate scope. The method provides a new way to construct linear and five- or six-membered ring moieties in bioactive molecules.

A direct cobalt-catalyzed oxidative coupling between C(sp²)–H in unactivated benzamides and C(sp³)–H in simple alkanes, ethers and toluene derivatives was explored.     

Oxidative cross-dehydrogenative coupling (CDC) via C(sp2)–H bond functionalization: tert-butyl peroxybenzoate (TBPB)-promoted regioselective direct C-3 acylation/benzoylation of 2H-indazoles with aldehydes/benzyl alcohols/styrenes

An efficient, cost-effective, transition-metal-free, oxidative C_(sp²)–H/C_(sp²)–H cross-dehydrogenative coupling via a C_(sp²)–H bond functionalization protocol for the regioselective direct C-3 acylation/benzoylation of substituted 2H-Indazoles 1a–m with substituted aldehydes 2a–q/benzyl alcohols 5a–e/styrenes 6a–e is reported. The operationally simple protocol proceeds in the presence of tert-butyl peroxybenzoate (TBPB) as an oxidant in chlorobenzene (PhCl) as a solvent at 110 °C for 24 h under an inert atmosphere, which furnished a diverse variety of substituted 3-(acyl/benzoyl)-2H-indazoles 3a–q/4a–l in up to 87% yields. The reaction involves a free-radical mechanism and proceeds via the addition of an in situ generated acyl radical (from aldehydes/benzyl alcohols/styrenes) on 2H-indazoles. The functional group tolerance, broad substrate scope, control/competitive experiments and gram-scale synthesis and its application to the synthesis of anti-inflammatory agent 11 and novel indazole-fused diazepine 13 further signify the versatile nature of the developed methodology.

An efficient transition-metal-free oxidative C_(sp²)–H/C_(sp²)–H cross-dehydrogenative coupling via C_(sp²)–H bond functionalization for regioselective C-3 acylation/benzoylation of 2H-indazoles with aldehydes/benzyl alcohols/styrenes is reported.     

In situ study on interactions between hydroxyl groups in kaolinite and re-adsorption water

The interactions between O–H groups in kaolinite and re-adsorption water is an important aspect that should be considered in the hydraulic fracturing method for the production of shale gas, because the external water adsorbed by kaolinite in shale would significantly affect the desorption of methane. In this study, the interactions were investigated via changing the amount of O–H groups and re-adsorption water in kaolinite by heating treatment and water re-adsorption. To overcome the overlap of IR vibration bands of the O–H functional groups in H₂O and those in parent kaolinite, kaolinite samples with D₂O re-adsorption were prepared by drying the H₂O from raw kaolinite and soaking the dried kaolinite in D₂O. The interactions between O–H groups in kaolinite and D₂O molecules were investigated by in situ DRIFT and TG-MS. The results demonstrated that the vibration at 3670 ± 4 cm⁻¹ in the DRIFT spectra could be due to the outer O–H groups of the octahedral sheet on the upper surface of the kaolinite microcrystal structure, rather than a type of inner-surface O–H group. All types of O–H groups, including the inner O–H groups in kaolinite, could be transformed into O–D groups after D₂O re-adsorption at room temperature. The inner-surface O–H groups in kaolinite are the most preferred sites for D₂O re-adsorption; thus, they would be the key factor for studying the effect of re-adsorption water on methane desorption. When the temperature increased from 100 °C to 300 °C, two layers of kaolinite slipped away from each other, resulting in the transformation of inner-surface O–H groups into outer O–H groups. Thus, the temperature range of 100 to 300 °C was suggested for the heat treatment of kaolinite to decrease the content of inner-surface O–H groups; thereby, the amount of re-adsorption water was reduced. However, to thoroughly remove the re-adsorption water, a temperature higher than 650 °C should be used.

Because two layers slipped away from each other, inner-surface O–H was transformed into outer O–H during heating from 100–300 °C. Re-adsorption water could be thoroughly removed at 650 °C.     

The green synthesis of a palm empty fruit bunch-derived sulfonated carbon acid catalyst and its performance for cassava peel starch hydrolysis

A sulfonated carbon acid catalyst (C–SO₃H) was successfully generated from palm empty fruit bunch (PEFB) carbon via hydrothermal sulfonation via the addition of hydroxyethylsulfonic acid and citric acid. The C–SO₃H catalyst was identified as containing 1.75 mmol g⁻¹ of acid and 40.2% sulphur. The surface morphology of C–SO₃H shows pores on its surface and the crystalline index (CrI) of PEFB was decreased to 63.8% due to the change structure as it became carbon. The surface area of the carbon was increased significantly from 11.5 to 239.65 m² g⁻¹ after sulfonation via hydrothermal treatment. The identification of –SO₃H, COOH and –OH functional groups was achieved using Fourier-transform infrared spectroscopy. The optimal catalytic activity of C–SO₃H was achieved via hydrolysis reaction with a yield of 60.4% of total reducing sugar (TRS) using concentrations of 5% (w/v) of both C–SO₃H and cassava peel starch at 100 °C for 1 h. The stability of C–SO₃H shows good performance over five repeated uses, making it a good potential candidate as a green and sulfonated solid acid catalyst for use in a wide range of applications.

A sulfonated carbon acid catalyst (C–SO₃H) was successfully generated from palm empty fruit bunch (PEFB) carbon via hydrothermal sulfonation via the addition of hydroxyethylsulfonic acid and citric acid.     

Iron catalyzed C–C dehydrogenative coupling reaction: synthesis of arylquinones from quinones/hydroquinones

An atom-economical approach for the synthesis of arylquinones was achieved successfully via direct oxidative C–C dehydrogenative coupling reaction of quinones/hydroquinones with electron-rich arenes using an inexpensive Fe–I₂–(NH₄)₂S₂O₈ system. The efficiency of this catalytic approach was established with a broad scope of substrates involving quinones and hydroquinones to give high yields (60–89%) of several arylated quinones. The present protocol is simple, practical, and shows good functional group tolerance.

The synthesis of arylquinones was achieved via direct oxidative C–H/C–H cross-coupling of quinones/hydroquinones with electron-rich arenes using Fe–I₂–(NH₄)₂S₂O₈ system involving quinones/hydroquinones to give high yields (60–89%) of arylquinones.     

Transition-metal-catalyzed remote C–H functionalization of thioethers

In the last decade, transition-metal-catalyzed direct C–H bond functionalization has been recognized as one of most efficient approaches for the derivatization of thioethers. Within this category, both mono- and bidentate-directing group strategies achieved the remote C(sp²)–H and C(sp³)–H functionalization of thioethers, respectively. This review systematically introduces the major advances and their mechanisms in the field of transition-metal-catalyzed remote C–H functionalization of thioethers from 2010 to 2021.

This minireview systematically introduces the major advances and their mechanisms in the field of transition-metal-catalyzed remote C–H functionalization of thioethers.