Design and synthesis of antiviral pseudo-natural products through effective one-step acylmethylation macrocyclization

Influenza virus poses a significant threat to global public health,causing serious repercussions on human life and social well-being.Over the past decades,various antiviral drugs targeting either the virus itself or its host were identified.However,the emergence of drug-resistant influenza virus strains has posed a critical challenge to the effectiveness of these existing anti-influenza agents .Consequently,there is an urgent need to develop novel molecules with new chemical frameworks.Macrocyclic natural products serve as a crucial resource for validating targets and discovering lead compounds.However,the number of naturlly crring macrocyclic natural products is limited due to inherent biosynthetic pathways,which restricts the development of macrocyclic drugs.In contrast,artificially synthesized pseudonatural products show enhanced availability and greater structural diversity,while possessing similar biological functions[5]and have attracted significant interest from medicinal chemists.Hence,it is valuable to develop effective synthetic methods to expedite the discovery of macrocyclic lead compounds.

Oxidative Stress in Collegiate Cross Country Skiers in Mid- and Post-Seasons

Purpose: The oxidative stress (OS) hypothesis of overtraining syndrome argues that increased production of free radicals through exercise cause muscle fatigue and damage resulting in lower athletic performance. Several studies have investigated OS immediately before and after exercise bouts in a training macrocycle. Our study aimed to compare OS of endurance athletes between a competition macrocycle and the immediate post-season recovery macrocycle. In addition, we aimed to identify athletes who experienced an unexplainable drop in athletic performance during the competition season in order to compare their OS to those who experienced no drop in performance. Methods: Fifteen members of the University of Alaska Fairbanks cross country ski team volunteered for this study. Blood samples were taken in early February (“mid-season”) and late April (“post-season”). Participants completed questionnaires regarding physical activity and athletic performance at the time of the blood draws. Plasma was analyzed for 4-hydroxynonenal (HNE), nitrotyrosine, nitric oxide (NOX), and superoxide dismutase (SOD). Significance was determined by Wilcoxon and Mann-Whitney tests. Results: Participants displayed significantly higher (p Conclusion: Signs of oxidative stress and mitigation during the post-season recovery macrocycle were higher in athletes who reported experiencing a drop in athletic performance during the competition season macrocycle.

Natural scaffolds-inspired synthesis of CF_(3)-substituted macrolides enabled by Rh-catalyzed C–H alkylation macrocyclization

The development of innovative strategies and methods to provide natural product-like macrocycles not accessible by biosynthesis, but endowed with novel bioactivities and simplified structure, is highly desirable. Inspired by the key scaffolds of rapamycin and FR252921, herein, we report a Rh(III)-catalyzed C–H alkylation macrocyclization, which enables access to CF_(3)-substituted macrolides. DFT calculations reveal that the chemoselectivity between C–H alkylation and olefination macrocyclization was highly controllable. Moreover, the unique CF_(3)-substituted macrolides showed potent anti-inflammation activities against TNF-α, IL-6 and CCL2 m RNA expression.

Structural characterization and mass spectrometry fragmentation signatures of macrocyclic alkanes isolated from a Sydney Basin torbanite,Australia

Individual hydrocarbons identified to be macrocyclic alkanes in a torbanite from the Sydney Basin(Australia)were successfully isolated from its extracts using preparative gas chromatography and analyzed by NMR.Saturated cyclic structures were confirmed by single peaks in the NMR~1H and~(13)C spectra indicating single forms of H and C atoms exist in these biomarker molecules.This is consistent with the methylene unit in a ring system assignment of the macrocyclic alkanes and accounts for a formula of(CH2)n.The unusual molecular structures of these compounds are consistent with those that were identified from previous GC retention index data and co-injection with a standard supports the previous research.The mass spectral fragmentation behaviors of representative cyclic alkanes were further investigated by comparing them with the mass spectra of isolated individual macrocyclic alkanes.The characteristic fragment ions in the macrocyclic alkanes of(M–28)+and base peaks of m/z 97,111,125,etc.,can be assigned as being generated by simple a-/i-cleavage and hydrogen rearrangement.These fragmentation pathways combined with retention indices should assist in differentiating these compounds from monounsaturated alkenes and alkylated monocyclics having similar mass spectral characteristics in other geological samples.

芳香聚芳醚酮大环化合物结构分析

Macrocyclic arylene ether ketone was characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrum(MALDI-TOF MS)combining with nuclear magnetic resonance(NMR)spectra.No any more fragment ionization peaks except for the molecular ion peak from the mass spectrum.The structure of macrocyclic dimmer was further affirmed by the NMR spectra through the analysis of chemical shifts.The MALDI-TOF MS combining with NMR technique was found an important tool to characterized Macrocyclic aromatic oligomers.

Synthesis of novel disulfide-bridged dilactam crown ethers

The novel macrocyclic dilactams with redox-switched disulfide linkage were synthesized. These compounds were obtained from 2,2′-dithiodibenzoyl chloride in the macrocyclization step by fast addition method in moderate yields.

Kansuinine J,a new macrocyclic diterpenoid from the roots of Euphorbia kansui

A new macrocyclic diterpenoid,named kansuinine J（1）,was isolated from the roots of Euphorbia kansui.Its structure was characterized on the basis of spectroscopic analysis.

Characterization, crystal structure and luminescence properties of a new europium(III) complex with macrocyclic ligand derived from 2,6-diformyl-4-methylphenol and diethylenetriamine

The title compound （13,27-dimethyl-3,6,9,17,20,23-hexaazatricyclo-[23.3.1.1^11,15]-triaconta-1 （29）,2,9,11,13,15（30）, 16,23,25,27- decaene-29,30-diol-N^3, N^6, N^9, O^29, O^30）-bis （nitrato-O,O＇）-europium （Ⅲ） nitrate hydrate （[EuL（NO3）2]（NO3）·H2O, L denotes the macrocyclic ligand） was prepared and characterized by elemental analysis, infrared spectra, and electrospray mass spectra. Its crystal and molecular structure was determined by X-ray diffraction. The crystal crystallized in the monoclinic system, space group C2/c with a=2.3757 （4） nm, b=1.4302（3） nm, c=1.9584（3） nm, β=91.654（5）°, M=818.60, V=6.651（2） nm^3, Z=8, D=1.635 g/cm, F（000）=3312, R=0.0542, wR=0.1045. The central ion Eu^3＋ was nine-coordinated in the coordinaton geometry of a distorted tricapped trigonal prism. The macrocycle was coordinated through two oxygen and three nitrogen atoms. Two nitrate are chelate in the opposite positions of the macrocycle, the third nitrate being ionic. At room temperature, excitation of the title complex gave rise to the characteristic emissions of the Eu^3＋ ion.

Synthesis of New Aza-crown Ethers Containing Pyridine Ring and their Liquid Membrane Transport of Alkali Cations

Five new aza-crown ethers have been prepared by the condensation of 2,6-bis[(2-formylphenyl)oxymethyl] pyridine with different diamino compounds in hot methanol, the bis-Schiff bases without isolation were reduced with NaBH4 to afford the corresponding aza-crown ethers. The liquid membrane transport or alkali cations using the five new macrocycles as the ion-carriers was also studied.

The First Example of Inorganic-organic Compound Involving the Largest Vanadium Cluster of [V_(34)O_(82)]^(10-): Hydrothermal Synthesis and Characterization of a One-dimensional Chain of {[NiC_(16)H_(36)N_4]_5[V_(34)O_(82)]}_n

The title compound, [NiL]5[V34O82·8H2O （1, L=5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane）, has been synthesized under hydrothermal conditions and structurally characterized by EA, IR, XPS, TG and single-crystal X-ray diffraction. It crystallizes in the monoclinic system, space group C2/c with a=33.061（4）, b=15.3457（17）, c=33.902（4）, β=101.930（2）°, Mr=4904.08, V=16828（3）3 , Z=4, Dc=1.936 g/cm3 , F（000）=9832, μ=2.425 mm-1 , the final R=0.0402 and wR=0.0969. The mixed valence vanadium clusters of [V34O82]10- bridges [NiL]2＋ to form a one-dimensional chain in 1. To the best of our knowledge, the title complex is the first example of organic-inorganic hybrid material involving the largest vanadium cluster of [V34O82]10-.

Catalytic hydrolysis of phosphate diester (BNPP) and plasmid DNA by mononuclear macrocyclic polyamine metal complexes

The activities of the catalytic hydrolysis of phosphate diester （BNPP） [bis（p-nitrophenyl）phosphate diester] and plasmid DNA （pUC 18） by mononuclear macrocyclic polyamine metal complexes have been investigated in this paper. The results showed that the highest activity in hydrolysis of BNPP was obtained with le--Zn（II） complex （composed of lipophilic group） as catalyst. The hydrolysis rate enhancement is up to 3.64 × 10^4 fold. These metal complexes could effectively promote the cleavage of plasmid DNA （pUC18） at physiological conditions.

Heterometallic Trinuclear Ni_2Zn and Ni_2Mn Complexes of Macrocyclic Oxamide: Synthesis and Crystal Structures

Two novel heterometallic trinuclear complexes of macrocyclic oxamide [Mn（NiL）2（HBTC）H2O] （1） and [Zn（NiL）2（HBTC）H2O] （2） （NiL, H2L = 2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclo-pentadeca-7,13-dien, H3BTC = 1,3,5-benzenetricarboxylic acid） have been solvothermally synthesized and structurally characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. For 1, the crystals crystallize in the monoclinic system, space group P21/c with a = 11.3595（5）, b = 23.1498（11）, c = 17.2558（8） and =101.2530（10）°. For 2, the crystals crystallize in the monoclinic system, space group P21/c with a = 11.5214（8）, b = 20.6566（14）, c = 18.4126（13） and = 92.6770（10）°. The structures of 1 and 2 have oxamido-bridged trinuclear [NiⅡ2MⅡ] units and consist of two-dimensional supramolecular architectures formed by strong O–H…O intermolecular hydrogen bonds.

Synthesis and structure determination of pyrazine-containing macrocyclic polyazomethines

Two pyrazine-containing macrocyclic polyazomethines 2 and 3 were synthesized by direct [2 ＋ 2] and [3 ＋ 3] condensation reactions between 2,21-[pyrazine-2,3-diylbis（oxy）]dibenzaldehyde （1） and hydrazine. Both 2 and 3 were characterized by NMR, HRMS, and their structures were determined via X-ray crystal diffraction studies.

Reinvestigation on the Reaction of Salicylic Chloride with Salicylic Amide and X-ray Crystal Structure of a New Macrocyclic Polyester

The reaction of salicylic chloride and salicylic amide at 170 ℃ gave benzoxazine and a new macrocyclic polyester 3, whose crystal structure has been determined by single-crystal X-ray diffraction analysis. Compound 3: C28H16O8, Mr = 480.41, monoclinic, space group P21/n, a = 15.353(3), b = 14.196(3), c = 21.147(4) ? b = 103.32(3), V = 4485(2) ?, Z = 8, F(000) = 1984, Dc = 1.423 g/cm3 and m = 0.106 mm-1. The final R = 0.0535 and wR = 0.1275 for 7903 observed reflections (I ≥ 2(I)). In the asymmetric unit of the compound there exist two independent molecules which are connected by weak aromatic CH…O hydrogen bonding between C(47)?H(47) and atom O(7) of the carbonyl group.

CLEMOCHINENOSIDE A, A MACROCYCLIC COMPOUND FROM CLEMATIS CHINENSIS

The structure of a new macrocyclic compound, clemochinenoside A obtained from Clematis chinensis was identified by NMR, FAB-MS, NOE and chemical hydrolysis.

Synthesis and Crystal Structure of a Macrocycle[Cu(dadm)(mal)(H_(2)O)]_(2)·2H_(2)O

The reaction of 4,4?-diaminodiphenylmethane (dadm), malonic acid (H2mal) and Cu(NO3)2 in aqueous solution results in a discrete binuclear Cu(II) macrocycle: [Cu(dadm)(mal)- (H2O)]22H2O. It crystallizes in monoclinic, space group P21/c with a = 15.231(3), b = 11.847(2), c = 9.801(2) ? b = 106.75(3)o, V = 1693.5(6) 3, Z = 2, C32H40Cu2N4O12, Mr = 799.76, Dc = 1.568 g/cm3, ?(MoKa) = 0.71073 ? = 1.325 mm-1, F(000) = 828, the final R = 0.0531 and wR = 0.1244 for 3421 observed reflections with I > 2s(I). Each Cu(II) is coordinated by two oxygen atoms from a mal ligand, two nitrogen atoms from two dadm ligands and a water oxygen atom to form a triangle bipyramidal motif. The title compound possesses a distorted macrocycle enclosed by dadm with approximate dimensions of 8.3 ??5.9 ?

The Determination of the Protonation Constants of A New Macrocyclic Dinucleating Ligand, BDBPH

The protonation constants of a new dinucleating 24-membered hexaazadiphenol macrocyclic ligand, BDBPH, were determined by potentiometric measurement at 25.0 degreesC and mu = 0.100 mol.L-1 (KCl). The species distributions of the deprotonated and protonated compounds in the pH range from 2 to 12 aqueous solutions were also described.

The Synthesis of a New Macrocyclic Dinucleating Ligand,3,6,9,17,20,23-Hexaaza-29,30-Dihydroxy-13,27-Dimethyl-Tricyclo[23,3,1,1^(11,15)]Triaconta-1(28),11,13, 15(30),25,26-Hexaene

A new dinucleating 24-membered hexaazadiphenol macrocyclic ligand, 3,6,9,17,20, 23-hexaaza-29,30- dihydroxy-13,27-dimethyl-tricycl [23, 3, 1, 1 11,15] triaconta -1(28), 11,13,15(30),25, 26-hexaene, BDBPH, was synthesized by the NaBH4 reduction of the Schiff-base obtained from the [2+2] condensation between diethylenetriamine and diformyl -p-cresol. The structure was characterized by elemental analysis, 1HNMR and FAB-MS. The synthetic method was also discussed.

Synthesis and Crystal Structure of Bis(dicyanamide) (5,7,7,12,14,14-Hexamethyl-1,4,8,11-tetraazacyclotetradecane) Nickel(Ⅱ)

The nickel(Ⅱ)complex [Ni(teta){N(CN)2}2] (teta = 5,7,7,12,14,14-hexamehyl-1,4, 8,11-tetraazacyclotetradecane) was synthesized and its structure has been determined by single- crystal X-ray diffraction. Crystal data: C20H36N10Ni, monoclinic, space group P21/c, a = 9.632(2), b = 11.833(2), c = 10.613(2) ? b = 93.46(3), V = 1207.4(4) ?, Mr = 475.30, Z = 2, Dc = 1.307 g/cm3, F(000) = 508, m(MoKa) = 0.831 mm-1, R = 0.0446 and wR = 0.1274 for 2423 observed reflections with I > 2s(I). The center nickel ion is coordinated by six nitrogen atoms, four from the macrocyclic ligand teta and the other two from two dicyanamides. The dicyanamide is coordinated to the metal atoms as uni-dentate manner via nitrile nitrogen atom.

Synthesis of aromatic-linked polyamine macrocyclic derivatives as HIV-1 entry inhibitors

A series of novel aromatic-linked polyamine macrocyclic derivatives have been synthesized. Their structures were confirmed by MS and ^1H NMR. These compounds exhibited potent anti-HIV-1 activities.