Conversion mechanism of heptachlor by a novel bacterial strain

Microbial treatment is the preferred method for the remediation of soil and water contaminated by heptachlor. We collected sludge samples from the sewage biological treatment pool of Shaanxi Insecticide Factory in Xi''an, China, which were used as bacteria source. With heptachlor as the substrate, at 30–35 °C, an effective microorganism (named strain H) for heptachlor degradation was isolated successfully after a long period of acclimation, screening and purification. Strain H was able to use heptachlor as a carbon source and had a good capacity for biodegradation of heptachlor. Strain H was preliminarily identified as a Gram-negative, short rod-shaped, single-cell bacterial strain that was similar to the genus Escherichia or Shigella, according to the analysis of its morphology and physiological–biochemical characteristics. Then, strain H was further identified as a novel bacterium based on the similarity analysis of its 16S rDNA gene sequence with the sequences logged in the RDP and GenBank databases. The 16S rDNA of this bacterium has never been reported before. When the inoculation volume and the pH were 20% and 7.1–7.6, respectively, the degradation rate of heptachlor can reach more than 88.2% in 130 h, with the initial concentration of heptachlor being 300 μg L⁻¹ at 30–35 °C. Identification of the metabolites by GC/MS showed that strain H degrades heptachlor via two pathways simultaneously, i.e., pathway (1) hydroxylation at the C1 position of heptachlor to 1-hydroxychlordene followed by epoxidation and dechlorination to chlordene epoxide; and pathway (2) epoxidation at the C2 and C3 positions of heptachlor to heptachlor epoxide, and then heptachlor epoxide was further transformed to chlordene epoxide by dechlorination reaction, or degraded to heptachlor diol by hydrolysis reaction. The biodegradation of heptachlor indicated that heptachlor and its metabolites can be converted into less-toxic small molecular metabolites by a series of reactions such as epoxidation, hydrolysis and dechlorination reactions.

Microbial treatment is the preferred method for the remediation of soil and water contaminated by heptachlor.     

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.     

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.     

Sarcosenones A–C,highly oxygenated pimarane diterpenoids from an endolichenic fungus Sarcosomataceae sp.

Three new highly oxygenated pimarane diterpenoids, sarcosenones A–C (1–3), and the known 9α-hydroxy-1,8(14),15-isopimaratrien-3,7,11-trione (4), were isolated from cultures of an endolichenic fungus Sarcosomataceae sp. Their structures were elucidated based on NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compound 1 showed moderate cytotoxicity against a small panel of four human tumor cell lines, with IC₅₀ values of 7.5–26.4 μM.

The new highly oxygenated pimarane diterpenoids sarcosenones A–C (1–3) were isolated from an endolichenic fungus Sarcosomataceae sp. Compound 1 showed moderate cytotoxicity towards human tumor cells.     

Catalytic,selective, and stereocontrolled construction of C4 quaternary and homobenzylic dihydroisoquinolones by sp3 C–H benzylation

C1 benzylated isoquinoline derivatives constitute the core of benzylisoquinoline alkaloids (BIAs). However, their C4 congeners remain elusive. Here, we describe a diastereoselective, catalytic, and modular C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds of readily affordable vicinally functionalized dihydroisoquinolones are replaced by sp³ C–benzyl bonds. The method provides expedient access to C4 quaternary and homobenzylic dihydroisoquinolones, which are attractive fragments for potential drug discovery.

A diastereoselective and catalytic C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds are replaced by sp³ C–benzyl bonds, leading to C4 quaternary and homobenzylic dihydroisoquinolones, is described.     

Regioselective O/C phosphorylation of α-chloroketones: a general method for the synthesis of enol phosphates and β-ketophosphonates via Perkow/Arbuzov reaction

A regioselective O/C phosphorylation of α-chloroketones with trialkyl phosphites was performed for the first time, which employed solvent-free Perkow reaction and NaI-assisted Arbuzov reaction under mild conditions respectively. Versatile enol phosphates were prepared in good to excellent yields as well as β-ketophosphinates.

A highly regioselective O/C phosphorylation of α-chloroketones with trialkyl phosphites was developed in the preparation of enol phosphates and β-ketophosphonates.     

The Reformatsky analogous reaction for the synthesis of novel β-thioxoesters via using aroyl isothiocyanates under solvent-free ball milling and conventional conditions

The classical Reformatsky reaction, initially described in 1887, is considered one of the most useful ways of forming C–C bonds. The target of this work includes improving the Reformatsky reaction between aroyl isothiocyanates and α-haloesters using metallic zinc to form β-thioxoesters (3–11). In this procedure, a new metal-mediated carbon–carbon linkage is formed with the formation of an organozinc halide and decomposition due to the presence of dilute acid, affording a good yield of the desired product via conventional techniques and ball milling. The Reformatsky reaction requires no solvent and no inert gases.

The Reformatsky analogous reaction between aroyl isothiocyanates and α-haloesters using metallic zinc to form β-thioxoesters via ball milling and conventional techniques.     

TDDFT-ECD and DFT-NMR studies of thaigranatins A–E and granatumin L isolated from Xylocarpus granatum

TDDFT-ECD calculations were utilized to explain the mirror image or different ECD spectra of previously reported homochiral natural products thaigranatins A–E and granatumin L, the simple comparison of which would result in a wrong stereochemical conclusion. The configurational assignment was confirmed independently and geometrical parameters of the chromophores governing the ECD spectra were identified in the structurally related natural products by analyzing the ECD spectra and geometries of the low-energy computed conformers obtained by different methods. Different conformations of the furan-2-yl-δ-lactone subunit were found responsible for the mirror image ECD spectra of the homochiral thaigranatins C–E. Two DFT ¹³C NMR chemical shift calculation methods and DP4+ analysis were performed on the C-6 epimers of thaigranatin D, which together with the ECD calculation, could determine the absolute configuration of C-6 as (R).

TDDFT-ECD calculations were utilized to explain the mirror image or different ECD spectra of thaigranatins A–E and granatumin L.     

Direct C–H functionalization of difluoroboron dipyrromethenes (BODIPYs) at β-position by iodonium salts

A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed, which provides facile access to a variety of mono-substituted BODIPY dyes. Interestingly, β-styryl BODIPY compound 9b exhibits apparent cytotoxicity after laser irradiation, which has great potential for photodynamic therapy.

A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed and β-styryl BODIPY 9b has great potential for photodynamic therapy.     

Functionalization of α-hydroxyphosphonates as a convenient route to N-tosyl-α-aminophosphonates

Direct conversion of the α-hydroxyl group by para-toluenesulfonamide to yield α-(N-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b–37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b–21a,b in the presence of K₂CO₃, via the retro-Abramov reaction of the appropriate aldehydes, 1–5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b–37a,b with better diastereoselectivity than in the case of the Pudovik reaction. The mechanism for this transformation is proposed herein. When Cbz N-protected aziridine 9a,b and phenylalanine analogue 12a,b were exploited, intramolecular substitution was observed, leading to the corresponding epoxide 38 as the sole product, or oxazolidin-2-one 39 as a minor product. Analogous substitution was not observed in the case of proline 18a,b and serine 21a,b derivatives.

The reaction mechanism and diastereoselectivity of the direct transformation of α-hydroxyphosphonates 6a,b–21a,b by para-toluenesulfonamide, yielding α-(N-tosyl)aminophosphonates 23a,b–37a,b under K₂CO₃ conditions are presented.     

Bimetallic aluminum complexes bearing novel spiro-phenanthrene-monoketone/OH derivatives: synthesis,characterization and the ring-opening polymerization of ε-caprolactone

A series of spiro-phenanthrene-monoketone/OH derivatives (L1–L6) were synthesized and fully characterized with ¹H/¹³C NMR spectroscopy and elemental analyses. By treating ligands with AlMe₃, oxygen-bridged binuclear aluminum complexes (Al1–Al6) were isolated and characterized by ¹H/¹³C NMR spectroscopy. The molecular structures of ligands (L2, L4 and L5) and complex Al1 were determined by single crystal X-ray diffraction. In the presence of benzyl alcohol (BnOH), these aluminum complexes demonstrated high efficiency towards the ring-opening polymerization of ε-caprolactone (ε-CL), resulting in PCL in a linear manner with the BnO-end group. In addition, complexes Al1 and Al5 exhibited good catalytic activities even without BnOH. Moreover, complexes Al3 and Al6 with the bulkier substituent of ⁱPr at the ortho-position of the arylamines demonstrated better catalytic activities than the analogs. Moreover, substituents on the backbone also affected catalytic behaviors.

Bimetallic aluminum complexes bearing novel spiro-phenanthrene-monoketone/OH derivatives were synthesized, and displayed good activity toward the ring-opening polymerization of ε-caprolactone.     

Cipadessains A–K,eleven limonoids from the fruits of Cipadessa cinerascens

Eleven new mexicanolide-type limonoids, cipadessains A–K (1–11), were isolated from the fruits of Cipadessa cinerascens (Pellegr) Hand.-Mazz. Their planar structures were determined based on IR, UV, 1D and 2D NMR spectra and HRESIMS data. The absolute configuration of 1 was elucidated by single-crystal X-ray diffraction using mirror Cu Kα radiation, and that of compounds 2–8 were determined by ECD analysis. Two mexicanolides bearing methoxybutenolide moiety originated from the furan ring 3 and 6, showed significant cytotoxicity against HepG2 cell line with IC₅₀ values of 5.23 ± 0.12, 8.67 ± 1.02 μM, respectively; and NO inhibitory activities in LPS-activated RAW 264.7 macrophages at nontoxic concentration (IC₅₀ 5.79 ± 0.18, 6.93 ± 0.89 μM, respectively).

Eleven new mexicanolide-type limonoids, cipadessains A–K (1–11), were isolated from the fruits of Cipadessa cinerascens (Pellegr) Hand.-Mazz.     

Synthesis and anticancer studies of Michael adducts and Heck arylation products of sesquiterpene lactones,zaluzanin D and zaluzanin C from Vernonia arborea

Sesquiterpene lactones containing α-methylene-γ-lactones, zaluzanin D 1 and zaluzanin C 2 were isolated from the leaves of Vernonia arborea. Several diverse Michael adducts (3–22) and Heck arylation analogs (23–34) of 1 have been synthesized by reacting with various amines and aryl iodides, respectively and were assayed for their in vitro anticancer activities against human breast cancer cell lines MCF7 and MDA-MB-231. Among all the synthesized analogs, Michael adducts 9 and 10 showed better anticancer activities as compared to 1. However, among these compounds, only 10 has minimal cytotoxic effect on normal breast epithelial MCF10A cells. Our detailed mechanistic studies reveal that compounds 9 and 10 execute their antiproliferative activity through induction of apoptosis and thereby inhibit the cancer cells proliferation and compound 10 could be a lead compound for designing potential anti-cancer compound.

Sesquiterpene lactones containing α-methylene-γ-lactones, zaluzanin D 1 and zaluzanin C 2 were isolated from the leaves of Vernonia arborea.     

Side-by-side comparison of Notch- and C83 binding to γ-secretase in a complete membrane model at physiological temperature

γ-Secretase cleaves the C99 fragment of the amyloid precursor protein, leading to formation of aggregated β-amyloid peptide central to Alzheimer''s disease, and Notch, essential for cell regulation. Recent cryogenic electron microscopy (cryo-EM) structures indicate major changes upon substrate binding, a β-sheet recognition motif, and a possible helix unwinding to expose peptide bonds towards nucleophilic attack. Here we report side-by-side comparison of the 303 K dynamics of the two proteins in realistic membranes using molecular dynamics simulations. Our ensembles agree with the cryo-EM data (full-protein Cα-RMSD = 1.62–2.19 Å) but reveal distinct presenilin helix conformation states and thermal β-strand to coil transitions of C83 and Notch100. We identify distinct 303 K hydrogen bond dynamics and water accessibility of the catalytic sites. The RKRR motif (1758–1761) contributes significantly to Notch binding and serves as a “membrane anchor” that prevents Notch displacement. Water that transiently hydrogen bonds to G1753 and V1754 probably represents the catalytic nucleophile. At 303 K, Notch and C83 binding induce different conformation states, with Notch mostly present in a closed state with shorter Asp–Asp distance. This may explain the different outcome of Notch and C99 cleavage, as the latter is more imprecise with many products. Our identified conformation states may aid efforts to develop conformation-selective drugs that target C99 and Notch cleavage differently, e.g. Notch-sparing γ-secretase modulators.

Distinct membrane dynamics and conformations of C83- and Notch-bound γ-secretase may aid the development of Notch-sparing treatments of Alzheimer''s disease.     

Initiation mechanisms and kinetic analysis of the isothermal decomposition of poly(α-methylstyrene): a ReaxFF molecular dynamics study

This study investigates the thermal decomposition initiation mechanisms and kinetics of poly(α-methylstyrene) (PαMS) under isothermal conditions, using molecular dynamics simulations with the ReaxFF reactive force field. The unimolecular pyrolysis simulations show that the thermal decomposition of the PαMS molecule is initiated mainly by carbon–carbon backbone cleavage in two types at random points along the main chain that leads to different intermediates, and is accompanied by depolymerization reactions that lead to the formation of the final products. The time evolution of typical species in the process of PαMS thermal decomposition at various temperatures presents specific evolution profiles and shows a temperature-dependence effect. Isothermal decomposition kinetic analysis based on PαMS pyrolysis shows that the activation energy varies with the degree of conversion during the thermal decomposition processes, which infers that the decomposition process at different conversions may have different reaction mechanisms.

Thermal decomposition of the PαMS molecule is initiated by random cleavage of the C–C backbone in two mechanism modes.     

Guaiane sesquiterpenes from the gorgonian Echinogorgia flora collected in the South China Sea

Echinoflorine (1), a new dimethylamino-substituted guaipyridine alkaloid with a novel γ-lactone-cyclohepta[c]pyridine fused skeleton, and three new guaiane sesquiterpene lactones, echinofloranolides A–C (2–4), together with eight known guaiane sesquiterpenes were isolated from the gorgonian Echinogorgia flora collected in the South China Sea. Their structures were elucidated by 1D and 2D NMR, HRESIMS, calculated ECD and DP4+ probability analyses.

Echinoflorine (1), a new dimethylamino-substituted guaipyridine alkaloid with a novel γ-lactone-cyclohepta[c]pyridine fused skeleton, and three new guaiane sesquiterpene lactones, echinofloranolides A–C (2–4), together with eight known guaiane sesquiterpenes were isolated from the gorgonian Echinogorgia flora collected in the South China Sea.     

Engineering pH-responsive switching of donor–π–acceptor chromophore alignments along a peptide nanotube scaffold

A cyclic tri-β-peptide cyclo(β-Ala-β-Ala-β-Lys) having diethylaminonaphthalimide at the β-Lys side chain (CP3Npi) self-assembled into a peptide nanotube in a solution of HFIP and water. CD spectra of the CP3Npi nanotubes show a negative Cotton effect at 441 nm and a positive Cotton effect at 393 nm, indicating that D–π–A naphthalimide chromophores are aligned in a left-handed chiral way along the nanotube. The CP3Npi nanotubes bear positive charges under acidic conditions retaining the nanotube structure but pH-responsive switching of D–π–A naphthalimide alignments along the nanotube between a left-handed chiral and random arrangement was observed. The peptide nanotube is a stable scaffold for attaining pH-responsive alignment switching of side-chain chromophores.

pH-Responsive switching between a left-handed chiral and random alignments of D–π–A naphthalimides along a peptide nanotube (PNT) composed of tri-β-cyclic peptides was attained in response to repeated pH changes.     

Regioselective Pd-catalyzed α-alkylation of furans using alkyl iodides

Herein, direct alkylation of the C–H bond at the α-position of furans catalyzed by palladium catalyst is reported. This protocol targets α-alkylfurans, achieving moderate to good yields under very practical reaction conditions. With a broad scope of substrates and good functional group tolerance, this method will has promising utility in medicinal chemistry.

A practical and regioselective strategy to synthesize α-alkylfurans via Pd-catalyzed direct C–H alkylation using alkyl iodides was developed.     

Exploring synthetic and therapeutic prospects of new thiazoline derivatives as aldose reductase (ALR2) inhibitors

Inhibition of aldose reductase (ALR2) by using small heterocyclic compounds provides a viable approach for the development of new antidiabetic agents. With our ongoing interest towards aldose reductase (ALR2) inhibition, we have synthesized and screened a series of thiazoline derivatives (5a–k, 6a–f, 7a–1 & 8a–j) to find a lead as a potential new antidiabetic agent. The bioactivity results showed the thiazoline-based compound 7b having a benzyl substituent and nitrophenyl substituent-bearing compound 8e were identified as the most potent molecules with IC₅₀ values of 1.39 ± 2.21 μM and 1.52 ± 0.78 μM respectively compared with the reference sorbinil with an IC₅₀ value of 3.14 ± 0.02 μM. Compound 7b with only 23.4% inhibition for ALR1 showed excellent selectivity for the targeted ALR2 to act as a potential lead for the development of new therapeutic agents for diabetic complications.

Inhibition of aldose reductase (ALR2) by using small heterocyclic compounds provides a viable approach for the development of new antidiabetic agents.     

Lanthanide complexes combined with chiral salen ligands: application in the enantioselective epoxidation reaction of α,β-unsaturated ketones

Readily available lanthanide amides Ln[N(SiMe₃)₂]₃ (Ln = Nd (1), Sm (2), Eu (3), Yb (4), La (5)), combined with chiral salen ligands H₂L^a ((S,S)-N,N′-di-(3,5-disubstituted-salicylidene)-1,2-cyclohexanediamine) and H₂L^b ((S,S)-N,N′-di-(3,5-disubstituted-salicylidene)-1,2-diphenyl-1,2-ethanediamine) were employed in the enantioselective epoxidation of α,β-unsaturated ketones. It was found that the salen–La complex shows the highest efficiency and enantioselectivity. A relatively broad scope of α,β-unsaturated ketones was investigated, and excellent yields (up to 99%) and moderate to good enantioselectivities (37–87%) of the target molecules were achieved.

The enantioselective epoxidation of α,β-unsaturated ketones was catalysed by readily available lanthanide amides La[N(SiMe₃)₂]₃ combined with chiral salen ligands.