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The reaction of 1-methyl-3,4-dihydroisoquinoline with phenacyl bromide and phenyl substituted phenacyl bromides have been carried out.The structure of the product of phenacyl bromide reaction has been unambiguously assigned as 5,6-dihydro-2-phenylpyrrolo<2,1-a>isoquinoline.

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Reactions of Cyclopropenones with Azomethines, VIII. Diphenylcyclopropenone and Cyclic Imines

Reactions of diphenylcyclopropenone (1a) and diphenyl cyclopropenethione (1b) with a variety of cyclic imines (derivatives of 3,4-dihydroisoquinolines 2-4, 2-substituted 1-pyrrolines 5 and 1-piperidines 6,7) gave rise to 2-pyrroline-4-ones and -4-thiones (8, 11, 16, 18, 21, 24, 25), derivatives of 1,3-thiazine (10, 17) and 1,3-oxazine (22, 26, 27), and 2-azabicyclo<3.1.0>hexane-3-ones and -3-thiones (28, 29).The spectroscopic and chemical properties of the products obtained were investigated.

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Application of Imine Reductases (IREDs) in Micro-Aqueous Reaction Systems

Here we present the applicability of different imine reductases (IREDs) in micro-aqueous reaction systems. Subjects of the study were the IREDs from Streptomyces aurantiacus (SaIR), Streptomyces sp. GF3587 (RGF3587IR), Streptomyces kanamyceticus (SkIR), Streptomyces ipomoeae 91-03 (SiIR), Streptomyces sp. GF3546 (SGF3546IR), and Paenibacillus elgii B69 (PeIR). The IREDs were overexpressed in Escherichia coli (E. coli) cells and used directly after lyophilization. Several organic solvents and buffer amounts were screened for the reduction of the two substrates beta-carboline harmane and 1-methyl-3,4-dihydroisoquinoline to the corresponding amines. Cyclopentyl methyl ether (CPME) proved to be the best solvent choice for the envisaged reduction. In addition, CPME is currently referred to as an environmentally benign solvent. Optimized reaction conditions were applied to 20 mM of the hardly water soluble substrates, leading to good conversions (up to 96%) and excellent enantiomeric excesses (>99%) in the best cases. The use of micro-aqueous reaction systems opens the way to further applications of IREDs with hardly water soluble substrates. (Figure presented.).

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The first catalytic, enantioselective aza-Henry reaction of an unactivated cyclic imine

The aza-Henry reaction is an efficient route to important chiral, vicinal diamines. Reports of the asymmetric version typically use electron-deficient acyclic imines. We report the first example of a catalytic, asymmetric aza-Henry reaction on an unfunctionalized cyclic imine that gives access to enantiopure diamine derivatives under experimentally straightforward conditions. The stereocentre is established through the initial nitromethane addition to the imine. The scalemic intermediate may be trapped through acylation, then crystallized. Copyright

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Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines

A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, and up to 15 g L-1 1-Me DHIQ was converted completely without a feeding strategy. Furthermore, the reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).

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SYNTHESIS AND PROPERTIES OF 8-AZA-D-HOMOGONANES WITH FUNCTIONAL SUBSTITUENTS AT C11

Annelation of 3,4-dihydroisoquinolines with 2-acyl-1,3-cyclohexanediones containing a terminal ester group in the acyl fragment yields 11-substituted derivatives of 8-aza-D-homogonanes.The compounds containing the 11-COOMe group exist in solution as a mixture of keto and enol tautomers with respect to C12 (up to 90percent of the latter).The 11-methoxycarbonylmethylene derivatives exist as a mixture of cis and trans isomers with respect to 9-H, whereas the 9,11-dimethyl derivative was isolated exclusively as the trans isomer.

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Effects of heartwood extractives on symbiotic protozoan communities and mortality in two termite species

Lower termites (Isoptera: Rhinotermitidae) are considered severe pests of wood in service, crops and plantation forests. Termites mechanically remove and digest lignocellulosic material as a food source. The ability to digest lignocellulose not only depends on their digestive tract physiology, but also on the symbiotic relationship between termites and their intestinal microbiota. The current study was designed to test the possible effects of four heartwood extractives (Tectona grandis, Dalbergia sissoo, Cedrus deodara and Pinus roxburghii) on the mortality, feeding rate and protozoan population in two lower termites, Reticulitermes flavipes and Heterotermes indicola. All wood extractives tested rapidly lowered protozoan numbers in the hindgut of termite workers, which was closely correlated with worker mortality. The average population of protozoans in both termite species was diminished in a dose-dependent manner after fifteen days feeding on treated filter paper. Mortality of termites increased when fed on filter paper treated with T. grandis or D. sissoo heartwood extractives with minimum feeding rate at the maximum concentration (10 mg ml?1). Protozoan number and termite survival was also compared with starved termites and results showed that protozoan populations ware reduced up to 99.60 and 65.71% in R. flavipes and H. indicola, respectively as compared to untreated filter paper controls with ? 80% survival for both termite species. Characterizations of heartwood extractives were performed using Gas Chromatography-Mass spectrometry (GC-MS) and chemical profiles were obtained for extractives from each wood species. The largest chemical components, based on percentage of sample, identified from T. grandis were Squalene, 2-methyl-9, 10-Anthracenedione and 1-Methyl-3,4-dihydroisoquinoline. Trismethoxyresveratrol, 1, 3-Diamino-8-n-butyl-5, 6 dihydrobenzoquinazoline and 6, 8-dimethyl-Benzanthracene were the largest components from D. sissoo. The largest percentage components from C. deodara were (E) ? Atlantone, Di-epi-alpha-cedrene and alpha-Cuprenene. The main components of P. roxburghii were identified as 1, 2, 3, 4-tetrahydro-5, 8-dimethyl-Acridin-9-amine, 2, 3-dihydro-5, 7-dihydroxy-2phenyl-4H-1-Benzopyran-4-one and 5-hydroxy-7-methoxy-2-phenyl4H-1-Benzopyran-4-one. These are discussed in terms of their termiticidal and protozoicidal properties.

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Opioid-salsolinol relationship in the control of prolactin release during lactation

Endogenous opioid peptides (EOP) and dopamine (DA)-derived salsolinol are implicated in the suckling-induced prolactin surge. The aim of this study was to investigate the relationship between the opioidergic and salsolinergic activity in the mediobasal hypothalamus of nursing sheep. The sheep were infused intracerebroventricularly with opioid receptors antagonists: naloxone (all types of receptors, n=6); naloxonazine (mu receptor, n=6) or the vehicle (control, n=6) in a series of five 30-min infusions (60 mug/60 mul) from 10:00 to 15:00, at 30-min intervals. The period of the experiment included the non-suckling (10:00-12:30) and suckling (12:30-15:00) periods. Simultaneously, a push-pull perfusion of the infundibular nucleus/median eminence was performed in every sheep to study the dopaminergic system activity. Blood samples were also collected at 10-minute intervals to determine plasma prolactin concentration. Both the mean perfusate salsolinol and plasma prolactin concentrations were higher during the suckling vs. non-suckling (P<0.001) period in the control. The perfusate DA concentration was below the detection limit in this group. Treatment with either naloxone or naloxonazine significantly (P<0.01) diminished plasma prolactin concentration, as compared with the controls and blocked the prolactin surge during suckling. In drug-infused sheep, the perfusate salsolinol concentration was below the detection limit but the increased DA and its metabolite 3,4-dihydroxyphenylacetic acid concentrations were observed. In conclusion, the stimulatory action of EOP on prolactin secretion in nursing females is mediated, at least in part, by salsolinol, and the ligands for mu opioid receptor may be the primary factors of this relationship, especially with respect to the suckling-induced prolactin surge. I hope this article can help some friends in scientific research. I am very proud of our efforts over the past few months and hope to 2412-58-0, help many people in the next few years.Formula: C10H11N

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Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells

Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonitoring of (¡À)-apomorphine hydrochloride total synthesis from 2-phenethylamine and 3,4-dimethoxybenzaldehyde against head and neck squamous cell carcinoma (HNSCC). Methods The cytotoxic effects of compounds against a panel of HNSCC cell lines were determined by PrestoBlue cell viability assay, while the genotoxicity of substances was evaluated by micronucleus test. Cell death was detected by flow cytometry (Annexin V/7AAD) and western blot analysis was used to detect the presence of cleaved Caspase-3 molecules. Results The aporphine and isoquinoline derivatives APO, C1, and A5 significantly reduced HNSCC cell viability and promoted DNA damages in these cells. Further, by activating the Caspase-3 pathway, these substances were able to induce apoptosis. Conclusion Our results revealed that APO, C1, and A5 exhibit cytotoxic effects in HNSCC cells. The mechanisms of action appear to be partly via the generation of DNA damages and apoptosis induction through Caspase-3 pathway activation. This study provides preclinical data that suggest a potential therapeutic role for APO, C1, and A5 against head and neck cancer cells.

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Additive-free pd-catalyzed alpha-allylation of imine-containing heterocycles

An additive-free Pd-catalyzed alpha-allylation of different imino-group-ontaining heterocycles is reported. The activation of alpha-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement.

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