- Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- And pyrrolo-fused polycyclic indoles from 2-formylpyrrole
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A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels–Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels–Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels–Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions in governing the endo stereocontrol.
- Camacho-Dávila, Alejandro A.,Delgado, Francisco,Escalante, Carlos H.,Espinoza-Hicks, Carlos,Martínez-Mora, Eder I.,Ramos-Morales, Fernando R.,Tamariz, Joaquín
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- Serendipitous base catalysed condensation-heteroannulation of iminoesters: a regioselective route to the synthesis of 4,6-disubstituted 5-azaindoles
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A serendipitous discovery of a novel one-pot synthesis of 4,6-disubstituted 5-azaindoles is reported herein. In the presence of Hunig's base, various N-substituted pyrrole-2-carboxaldehydes have been efficiently transformed into their corresponding 4,6-disubstituted 5-azaindoles through an imine mediated cascade condensation-heteroannulation. The synthetic value of the methodology is established by preparing a novel chemical analogue of a cannabinoid receptor type 2 (CB2) agonist.
- Chelvam, Venkatesh,Dudhe, Premansh,Pathak, Biswarup,Venkatasubbaiah, Krishnan
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supporting information
p. 1582 - 1587
(2020/03/06)
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- Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents
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Using matrine (1) as the lead compound, a series of new 14-(N-substituted-2-pyrrolemethylene) matrine and 14-(N-substituted-indolemethylene) matrine derivatives was designed and synthesized for their potential application as anticancer agents. The structure of these compounds was characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (SMMC-7721, A549 and CNE2). The results revealed that compound A6 and B21 displayed the most significant anticancer activity against three cancer cell lines with IC50 values in range of 3.42–8.05 μM, which showed better activity than the parent compound (Matrine) and positive control Cisplatin. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound A6 and B21 could significantly induce the apoptosis of SMMC-7721 and CNE2 cells in a dose-dependent manner. The cell cycle analysis also revealed that compound A6 could cause cell cycle arrest of SMMC-7721 and CNE2 cells at G2/M phase.
- Li, Zheng,Luo, Mengyang,Cai, Bin,Wu, Lichuan,Huang, Mengtian,Haroon-Ur-Rashid,Jiang, Jun,Wang, Lisheng
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supporting information
p. 677 - 683
(2018/02/06)
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- Palladium-Catalyzed Fluoroarylation of gem-Difluoroalkenes
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A Pd-catalyzed fluoroarylation of gem-difluoroalkenes with aryl halides is reported. By taking advantage of the in situ generated α-CF3-benzylsilver intermediates derived from the nucleophilic addition of silver fluoride to gem-difluoroalkenes, this strategy bypasses the use of a strong base, thus enabling a mild and general synthetic method for ready access to non-symmetric α,α-disubstituted trifluoroethane derivatives.
- Tang, Hai-Jun,Lin, Ling-Zhi,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 9872 - 9876
(2017/08/08)
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- Pd-Catalyzed Autotandem Reactions with N-Tosylhydrazones. Synthesis of Condensed Carbo- and Heterocycles by Formation of a C-C Single Bond and a C-C Double Bond on the Same Carbon Atom
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A new Pd-catalyzed autotandem reaction is introduced that consists of the cross-coupling of a benzyl bromide with a N-tosylhydrazone followed by an intramolecular Heck reaction with an aryl bromide. During the process, a single and a double C-C bond are formed on the same carbon atom. Two different arrangements for the reactive functional groups are possible, rendering great flexibility to the transformation. The same strategy led to 9-methylene-9H-fluorenes, 9-methylene-9H-xanthenes, 9-methylene-9,10-dihydroacridines, and also dihydropyrroloisoquinoline and dihydroindoloisoquinoline derivatives.
- Paraja, Miguel,Valdés, Carlos
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supporting information
p. 2034 - 2037
(2017/04/27)
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- Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class i and IIb histone deacetylase inhibitors
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A novel series of HDAC inhibitors demonstrating class I and IIb subtype selectivity have been identified using a scaffold-hopping strategy. Several designed compounds showed better selectivity for class I and IIb over class IIa HDAC isoforms comparing to the FDA approved HDAC targeting drug SAHA. A representative lead compound 22 bearing a biphenyl moiety demonstrated promising class I and IIb HDAC isoforms selectivity and in vitro anticancer activities against several cancer cell lines. This work could serve as a fundamental platform for further exploration of selective HDAC inhibitors using designed molecular scaffold.
- Yao, Yiwu,Liao, Chenzhong,Li, Zheng,Wang, Zhen,Sun, Qiao,Liu, Chunping,Yang, Yang,Tu, Zhengchao,Jiang, Sheng
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supporting information
p. 639 - 652
(2015/02/19)
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- Oxidative radical cyclization to pyrroles under reducing conditions. Reductive desulfonylation of α-sulfonylpyrroles with tri-n-butyltin hydride
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1-(2-Bromobenzyl)-2-alkanesulfonylpyrroles (1c, 1d) and 1-(4-bromobutyl)-2-methylsulfonylpyrrols (8) undergo oxidative radical cyclization with partial or complete reductive desulfonylation to the pyrrolizidine derivatives 5 and 9 by an AIBN initiated reaction with tri-n-butyltin hydride.These cyclizations are suggested to proceed via a pseudo SRN1 process involving radical addition to the α position of the pyrrole nucleus not bearing the sulfonyl group.Reductive removal of the alkylsulfonyl moiety is proposed to occur in a second process after completion of the oxidative radical cyclization.The site of the radical addition is supported by deuterium labelling studies.Consistent with the timing of the loss of the sulfonyl group is that 2-alkylsulfonylpyrroles 11 are reductively desulfonylated under the same conditions that effect the oxidative radical cyclizations.
- Antonio, Yulia,Cruz, Ma. Elizabeth De La,Galeazzi, Edvige,Guzman, Angel,Bray, Brian L.,et al.
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