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Synthesis and stereochemistry of 8,13-diaza-2,3-dimethoxygona-1,3,5(10),9(11)-tetraen-12-one and D-homo derivatives

From the condensation reaction of O-methylbutyrolactim (2), O-methylvalerolactim (3), O-methylcaprolactim (4) and O-methyl-4-t-butylcaprolactim (5) with ethyl 6,7-dimethoxy-alpha-<1,2,3,4-tetrahydro-isoquinoyl)>acetate (1), 8,13-diaza-2,3-dimethoxygona-1,3,5(10),9(11)-tetraen-12-one (6) D-homo-derivatives (7-9), and medium sized ring cyclic diamides (10,11) were obtained.The stereoselective reduction of compounds 6-9 by Adam’s platinum catalyst afforded 8,13-diaza-2,3-dimethoxygona-1,3,5(10)-trien-12-one (12) and its D-homo derivatives (13-15).The structures of thecompounds obtained were established by NMR and X-ray crystallographic analyses. – Keywords: 8,13-diazasteroids; stereochemistry; X-ray structure analysis

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Comparative study on alkaloids and their anti-proliferative activities from three Zanthoxylum species

Background: Alkaloids have been considered as the most promising bioactive ingredients in plant species from the genus Zanthoxylum. This study reports on the compositions and contents of the Zanthoxylum alkaloids (ZAs) from three Zanthoxylum species, and their potential anti-proliferation activities. Methods: An HPLC-UV/ESI-MS/MS method was established and employed to analyze the alkaloids in different Zanthoxylum extracts. The common and unique peaks and their relative contents were summarized and compared to evaluate the similarity and dissimilarity of the three Zanthoxylum species. Meanwhile, inhibitory activity tests to four carcinoma cell lines, i.e., stomach tumor cells (SGC-7901), cervical tumor cells (Hela), colon tumor cells (HT-29) and Hepatic tumor cells (Hep G2), were carried out in vitro to evaluate the bioactivities of the ZAs. Results: Seventy peaks were detected in the crude total alkaloid samples, and 58 of them were identified. As a result, 13 common peaks were found in the extracts of all the three Zanthoxylum species, while some unique peaks were also observed in specific species, with 17 peaks in Z. simulans, 15 peaks in Z. ailanthoides and 11 peaks in Z. chalybeum, respectively. The comparison of the composition and relative contents indicated that alkaloids of benzophenanthridine type commonly present in all the three Zanthoxylum species with high relative contents among the others, which are 60.52% in Z. ailanthoides, 30.52% in Z. simulans and 13.84% in Z. chalybeum, respectively. In terms of activity test, Most of the crude alkaloids extracts showed remarkable inhibitory activities against various tumor cells, and the inhibitory rates ranged from 60.71 to 93.63% at a concentration of 200 mug/mL. However, SGC-7901 cells seemed to be more sensitive to the ZAs than the other three cancer cells. Conclusion: The alkaloid profiles detected in this work revealed significant differences in both structures and contents among Zanthoxylum species. The inhibitory rates for different cancer cells in this study indicated that the potential anti-cancer activity should be attributed to quaternary alkaloids in these three species, which will provide great guidance for further exploring this traditional medicinal resource as new healthcare products.

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Recent Progress in Heterogeneous Asymmetric Hydrogenation of C=O and C=C Bonds on Supported Noble Metal Catalysts

The ease of separation, simple regeneration, and the usually high stability of solid catalysts facilitating continuous production processes have stimulated the development of heterogeneous asymmetric hydrogenation catalysis. The simplest and so far most promising strategy to induce enantioselectivity to solid metal catalysts is their modification by chiral organic compounds, as most prominently represented by the cinchona-modified Pt and Pd catalysts for the asymmetric hydrogenation of activated C=O and C=C bonds. In this Review, we provide a systematic account of the research accomplished in the past decade on noble metal-based heterogeneous asymmetric hydrogenation of prochiral C=O and C=C bonds, including all important facets of these catalytic systems. The advances made are critically analyzed, and future research challenges are identified.

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Application of the intramolecular alpha-amido-alkylation reaction for the synthesis of dibenzo [a,h] quinolizines

5,6,9-Trihydro-8H-dibenzo [a,h] quinolizin-8-ones 6 are obtained from adducts of 3,4-dihydroisoquinolines 1 and phenylacetyl chlorides as a result of an intramolecular alpha-amidoalkylation reaction.

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STRUCTURE AND PROPERTIES OF 8-AZASTEROIDS SYNTHESIZED BY REGIO- AND STEREOSELECTIVE ANNELATION OF 3,4-DIHYDROISOQUINOLINES BY ASYMMETRIC 2-ACYL-1,3-CYCLOHEXANEDIONES

It was found that annelation of 3,4-dihydroisoquinolines by 2-acyl-1,3-cyclohexanediones takes place regio- and stereoselectively, leading to C(11)- and C(17)-substituted derivatives of the 8-aza-D-homogonane series with a trans-disposition of the substituents (Me, Br, Cl, COOMe) at the above positions relative to the angular substituent (H, Me) at C(9). It was shown that the C(17)-halogen and methoxycarbonyl derivatives exist in crystals in the form of one stereoisomer, while in solutions as a mixture of stereoisomers, caused by a keto-enol tautomerism of the C(17a)-carbonyl. In solutions of acids, these derivatives exist in N(8)-…-C(17a) immonium-enol form, as one stereoisomer. It was found that the C(11)-methyl derivatives are obtained in the form of two restrained conformers with respect to ring C, which on boiling are reduced to one conformer. The assignment of the enol regiomers of 4-substituted 2-acetyldimedones has been carried out.

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The synthesis of 13-spiro-substituted protoberberines via the tandem addition – Cyclisation reaction of 3-methoxyphthalide anions to 3,4-dihydroisoquinolines

The reaction of the anion of 3-methoxyphthalide with 3,4-dihydroisoquinolines affords 13-spiro-substituted protoberberines rather than the expected 8,13-dioxo derivatives. Whilst the parent 3,4-dihydroisoquinoline reacts stereospecifically to yield the (13S*,13aS*) diastereomer, the 1-methyl derivative affords exclusively the (13R*,13aS*) isomer. This change in stereochemical outcome is attributed to conformational changes induced by the methyl group in the putative 8,13-dioxo-intermediates.

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Diastereoselective Kinetically and Thermodynamically Controlled Additions of (R)-(+)-Methyl p-Tolyl Sulphoxide Anion to Imines (Tolyl = C6H4Me)

The anion of (R)-(+)-methyl p-tolyl sulphoxide reacts diastereoselectively with imines to give chiral beta-amino sulphoxides.

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Benzytriphenylphosphonium borohydride (BTPPB) as a selective reducing agent for reduction of imines, enamines, and reductive amination of aldehydes with primary and secondry amines in methanol

Benzyltriphenyltriphenylphosphonium borohydride (BTPPB) (1) generated as white solid from benzyltriphenylphosphonium chloride and sodium borohydride is found to be a selective and versatile reducing agent. The reagent in methanol is very useful for reduction of imines, enamines and reductive animation of aldehydes.

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Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents

Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects.

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Tetrabenazine intermediate as well as synthesis method and application thereof as, well as intermediate product for synthesis (by machine translation)

The invention belongs to, the field of drug synthesis, and particularly relates to a butanaphenazine, intermediate and a synthesis method, thereof, as well as a synthesis: method 3,4 – thereof; and, 6,7 . (by machine translation)

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