Synthesis and Pregnancy Terminating Activity of 2-Aryl imidazo [2,1-a] isoquinolines

Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysis. They both showed high activities in NIH mice.

Efficient Synthesis of Isoquinolines by AgNO3-Catalyzed Sequential Imination-Annulation of 2-Alkynyl Aldehydes with Ammonium Bicarbonate

An operationally simple approach for the tandem synthesis of isoquinolines by the reaction of o-alkynylalde- hydes with ammonium bicarbonate via Ag-catalyzed 6-endo-dig ring closure is described. The reaction conditions and the scope of the reaction are examined, and a variety of substituted isoquinolines are prepared in moderate to excellent yields.

Design, Synthesis and Pregnancy-Terminating Activity of 2-Aryl Imidazo[2,1-a]isoquinolines

In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanical calculation and multiple regression analysis. A Good correlation equation was obtained (r2=0.925, q2=0.871). Some new compounds were designed according to the equation. Two of them, compounds 21 and 22, were synthesized and evaluated in NIH mice. The results showed that the difference of activity between 21 (median effective dose ED50=0.943 mg/kg/day) and 22 (ED50=1.099 mg/kg/day) was small and both of them were potent. It is also agreed with the computational results. Compared with L14105 which is the most potent pregnancy-terminating agent, these two compounds possess high activity. The evaluation of the anti-implanting activity showed that they were 100% effective at tested dosage 50.0, 25.0, 12.5 mg/kg/day×3 days in oral administration, which proved the both of them had anti-implanting activity and low first-pass effects.

Reactivity of 1-methylisoquinoline synthesis of pyrazolyl triazoloisoquinoline and thia-diazolyl isoquinoline derivatives

The reaction of 1-methylisoquinoline 1 with hy-drazonoyl halides 2 in ethanol in the presence of chitosan under microwave irradiation affords triazoloisoquinoline 4. Product 4 reacts with dimethylformamide-dimethylacetal to give ena- minones 7 which react with hydrazonoyl halides to give pyrazolyl triazoloisoquinoline 13. Also, 1-methylisoquinoline 1 reacts with arylisothio-cyanate to give thioanilide 15 which reacts with hydrazonoyl halides to give the corresponding thiadiazolyl isoquinoline derivatives 20, 24.

A new isoquinoline derivative from the leaves of Magnolia sieboldii K.Koch

Magnoline（1）,a new isoquinoline derivative,was isolated from the leaves of Magnolia sieboldii K.Koch（Magnoliaceae）.Its structure was elucidated on the basis of spectral analysis including 1D,2D NMR and HR-TOF-MS.

Analysis of isoquinoline alkaloids from Mahonia leschenaultia and Mahonia napaulensis roots using UHPLC-Orbitrap-MSn and UHPLC-QqQ LIT-MS/MS

Mahonia leschenaultia（ML） and Mahonia napaulensis（MN） are less known and unexplored medicinal plants of the family Berberidaceae. They are used by the Todas of Nilgiris in their religious and medical practices but chemically less identified. Hence, we decided to do extensive phytochemical analysis to explore the potential of these plant extracts. An ultrahigh performance electrospray tandem mass spectrometry（UHPLC-ESI-MS/MS）method was successfully developed for qualitative analysis of the bioactive components in Mahonia species using Orbitrap Velos Pro mass spectrometer. Sixteen compounds were identified by comparison of their retention times and mass spectra（MS） with authentic standards and reported literature. Multi-stage mass spectra（MS（2-8）） for the identification of protoberberine and aporphine alkaloids showed the sequential expulsion of all the substituents attached with their basic skeleton followed by CO loss. Eight of the identified compounds（berberine, jatrorrhizine, palmatine, magnoflorine, isocorydine, glaucine, tetrahydropalmatine and tetrahydroberberine） were simultaneously determined by another UHPLC-ESI-MS/MS method under the multiple reactions monitoring（MRM） mode quantitatively using triple quadrupole linear ion trap mass spectrometer. The analytical method was validated for 8 bioactive compounds with overall recovery in the range98.5%-103.6%（RSD≤2.2%）, precise（RSD≤2.07%） and linear（r≥0.9995） over the concentration range of 0.5-1000 ng/mL and successfully applied in ML and MN roots, which suggests the suitability of the proposed approach for the routine analysis of Mahonia species and their quality control.

Amides,Isoquinoline Alkaloids and Dipeptides from the Aerial Parts of Piper mullesua

One undescribedamide,pipermullesine A,twoundescribed isoquinoline alkaloids,pipermullesinesBand C,and six undescribed dipeptides,pipermullamides A–F,along with 28 known compounds,were isolated from the aerial parts of Piper mullesua.The structures of the undescribed compounds were elucidated based on the analysis of 1D and 2D NMR and MS data.Furthermore,the structures of pipermullesines A–Cwere confirmed by single crystal X-ray diffraction analysis.All isolates were evaluated for inhibitory activity against platelet aggregation induced by thrombin(IIa)or platelet-activating factor(PAF).(-)-Mangochinine,pellitorine,and(2E,4E)-N-isobutyl-2,4-dodecadienamide showed weak inhibitory activity against rabbit platelet aggregation induced by PAF,with IC_(50)values of 470.3μg/mL,614.9μg/mL,and 579.7μg/mL,respectively.

Efficient One-pot Synthesis of Pyrrolo[2,1-a]isoquinoline and Pyrrolo[1,2-a]quinoline Derivatives

A one-pot sequential reaction for efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a]quinoline derivatives has been developed.The reaction included firstly the Cu-catalyzed three-component reaction of isoquinoline（quinoline）,acetylenedicarboxylate and alkynylbenzene and then Cs 2 CO 3-promoted intramolecular cyclization reaction of initially formed 1-alkenyl-2-alkynyl-1,2-dihydroisoquinoline（1,2-dihydroquinoline）.

A Facile Synthesis and Crystal Structure of 1-Amino-3-(2′-methylphenyl)isoquinolin Hydrochloride

The title compound （C16H15ClN2） has been synthesized by a facile self-condensation of o-tolunitrile promoted by potassium tert-butanolate in DMPU, and its structure was characterized by ^1H NMR, ^13C NMR, IR, UV, HRMS and X-ray single-crystal diffraction. The crystal belongs to orthorhombic, space group Pna21 with a = 19.560（3）, b = 7.8500（14）, c = 18.428（3） A^°, Dc = 1.271 g/cm^3, Z= 8, 2 = 0.71073 A^°,μ（MoKa） = 0.257 mm^-1, Mr = 270.75, V= 2829.5（8） A^°^3, Flack parameter = 0.12（12）, F（000） = 1136, the final R = 0.0571 and wR = 0.1445 for 2701 observed reflections with I 〉 20（I）. The intermolecular N-H…Cl hydrogen bonds link the molecules into a one-dimensional chain running along axis a.

Radical cascade cyclization for the green and simple synthesis of silylated indolo[2,1-a]isoquinoline derivatives via visible light-mediated Si–H bonds activation

Photocatalytic and photoinduced silyl radicals cascade cyclization procedures for the green and simple preparation of fused tetracyclic skeleton silylated indolo[2,1-a]isoquinoline-6(5H)-ones from 2-aryl-N-acryloyl indoles with hydrosilanes are developed.The photocatalytic reaction is carried out with 9,10-dicyanoanthracene(DCA)as an organophotocatalyst and 3-acetoxyquinuclidine as hydrogen atom transfer(HAT)catalyst at room temperature under metal-and oxidant-free conditions.The keys to the success of photoredox-catalytic conversion include(1)the reductive quenching of DCA^(*)[E_(1/2)(*P/P^(-))=+1.97 V vs.SCE in MeCN]by 3-acetoxyquinuclidine(E_(p)=+1.22 V vs.SCE in MeCN),and(2)the thermodynamic feasibility of hydrogen atom abstraction from hydridic Si-H bond by electrophilic N^(+·).Particularly,the simple photoinduced cascade cyclization using(TMS)3SiH with 2-aryl-N-acryloyl indoles was exploited via an electron-donor-acceptor(EDA)complex under visible light irradiation.

Palladium-catalyzed carbonylative cyclization of alkene-tethered indoles with phenols or arylboronic acids:Construction of carbonyl-containing indolo[2,1-a]isoquinoline derivatives

A novel palladium-catalyzed carbonylative cyclization of alkene-tethered indoles with phenols or arylboronic acids is described,which provides a facile approach to access indolo[2,1-a]isoquinoline scaffolds.This method employs benzene-1,3,5-triyl triformate(TFBen)as the CO surrogate for the incorporation of a carbonyl group into indolo[2,1-a]isoquinoline scaffolds,and a variety of carbonyl-containing indolo[2,1-a]isoquinoline derivatives are prepared in good yields.

Effects of Metal Cations and Counter Anions on the Structural Stability of Isoquinoline-Based Metallo-Supramolecular Cages

Metallo-supramolecular architectures that are constructed by coordination-driven self-assembly have received tremendous attention on account of their diverse yet molecular-level precise structures and broad applications.Of particular,metal cations and counter anions are fundamentally important in terms of self-assembly,characterization and property;however,their effects on the structural stabilities of metallo-supramolecular architectures have seldom been investigated.To address this issue,herein,a series of octahedral metallo-cages that are capable of tolerating with five metal cations(Pd^(2+),Cu^(2+),Ni^(2+),Co^(2+)and Zn^(2+)),and five counter anions(ClO_(4)^(–),OTf^(–),BF_(4)^(–),NTf_(2)^(–)and NO_(3)^(–))are constructed by the coordination-driven self-assembly of a well-designed tritopic isoquinoline-based ligand with corresponding metal salts.Structural stability studies show that metal cations and counter anions play a critical role in the stability of the resulting cages depending on their coordination abilities and stacking manners.This work provides deep insights in the ever-diversifying field of metallo-supramolecular chemistry,and will enable us to design more sophisticated assembled structure with desired function.

Diversity-oriented synthesis of blue emissive nitrogen heterocycles and their conjugation with carbon nano-onions

The search for new fluorescent molecules for possible applications as functional p-electron systems and their conjugation with different nanomaterials is nowadays of paramount importance to broaden the availability of materials with different properties.Herein we present a diversity-oriented approach to heterocyclic luminophores based on a multicomponent Ugi reaction followed by a Pd-mediated cascade sequence.The new molecules are coupled to carbon nano-onions,and hybrid systems represent the first example of blue emitters conjugated with these carbon nanoparticles.

Chemical Constituents of Plants from Tribe Chelidonieae and their Bioactivities

The tribe Chelidonieae comprises 23 species of eight genera with an extensive distribution and a long medicinal usage history both in China and Western countries. A large number of chemical constituents have been isolated and identified from the species in tribe Chelidonieae, such as alkaloids, organic acids, and their derivatives, aromatics, triterpenoids, sterols, essential oils, and proteins, most of which possess a variety of bioactivities, especially for the antibacterial, anti-inflammation, antitumor, analgesia, anti-oxidation, and antiparasitic activity. Meanwhile, potential toxicities have been discovered in some constituents. Therefore, the species in tribe Chelidonieae have become a rich source for new drug discovery, biologic study, and mechanism research. This paper presents comprehensive information of the chemical constituents, pharmacological and toxicological research on the plants in tribe Chelidoieae, which is a reference for the plants in this tribe for further development.

Efficient Synthesis of Pyrrolo[2,1-a]isoquinoline and Pyrrolo[1,2-a]quinoline Derivatives via One-pot Two- step Metal-catalyzed Three-component Reactions

A sequential one-pot two-step reaction for efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a]- quinoline derivatives in good yields has been successfully developed. The reaction included firstly Cu-catalyzed three-component reaction of isoquinoline （quinoline）, acetylenedicarboxylate and alkynylbenzene and then Pd-catalyzed intramolecular C（sp）-C（sp^2） coupling reaction of initially formed 1-alkenyl-2-alkynyl- 1,2-dihydroiso- quinoline （1,2-dihydroquinoline）.

Tandem synthesis of functionalized hexaalkyl benzoisoquinolinopyrrolonaphthyridine-hexacarboxylate, via isoquinoline based multi-component reaction

An expedient,synthetic method to fused polycyclic derivatives of isoquinoline is described via tandem reaction of isoquinoline,dialkyl acetylenedicarboxylates and dialkyl chloromalonate.

Tungstophosphoric acid catalyzed synthesis of N-sulfonyl-1,2,3,4-tetrahydroisoquinoline analogs

An operationally simple and eco-friendly protocol has been developed for the synthesis of N-sulfonyl- 1,2,3,4-tetrahydroisoquinolines 3 using the modified Pictet-Spengler reaction of N-sulfonylphenylethy- lamines 1 and various aldehydes 2 in the presence of tungstophosphoric acid hydrate.

Pd(II)and Rh(III)Complexes with Isoquinoline Derivatives Induced Mitochondria-Mediated Apoptotic and Autophagic Cell Death in HepG2 Cells

Nonplatinummetal complexes of[Pd(L^(1))Cl_(2)](C1),[Rh(L^(1))Cl_(3)(DMSO)](C2),[Pd(L^(2))Cl_(2)](C3),and[Rh(L^(3))Cl_(3)(DMSO)](C4)with isoquinoline derivatives have been prepared and characterized.C1-C4 exhibited higher in vitro anticancer activity and lower toxicity than the corresponding ligands and cisplatin against HepG2 cells.The mechanistic studies revealed that C1 arrested the cell cycle at S-phase by regulation of cyclin and cyclin-dependent kinases.C1 was accumulated in mitochondria,which increased the generation of reactive oxygen species(ROS)and endoplasmic reticulum(ER)-stress response through mitochondrial dysfunction.Moreover,C1 stimulated Ca^(2+)release,activated the caspase cascade,and triggered mitochondria-mediated apoptosis.The in vivo studies of C1 demonstrated higher safety than cisplatin and effective tumor growth inhibition.C1 is a potential anticancer drug candidate.