β-Phenylethylamines and the isoquinoline alkaloids

Bentley, K. W.

doi:10.1039/b316108k

Cited by 154 publications

(46 citation statements)

References 111 publications

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“…alpha arylation | heterocycle | isoquinoline-N-oxide | one-pot T he isoquinoline motif and its derivatives form the cores of numerous natural products (1,2), are the central components of a number of pharmaceutical agents (3)(4)(5), and can provide the scaffold for chiral ligands (6,7) and valuable organic materials (8). However, traditional isoquinoline syntheses such as the Bischler-Napieralski (9, 10), Pictet-Spengler (11,12), and Pomeranz-Fritsch reactions (13)(14)(15) all centre around the lynchpin of electrophilic aromatic substitution and are thus often limited to electron-rich carbocycles (Scheme 1A).…”

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confidence: 99%

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

Donohoe

Pilgrim

Jones

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The utilization of sequential palladium-catalyzed α-arylation and cyclization reactions provides a general approach to an array of isoquinolines and their corresponding N-oxides. This methodology allows the convergent combination of readily available precursors in a regioselective manner and in excellent overall yields. This powerful route to polysubstituted isoquinolines, which is not limited to electron rich moieties, also allows rapid access to analogues of biologically active compounds.T he isoquinoline motif and its derivatives form the cores of numerous natural products (1, 2), are the central components of a number of pharmaceutical agents (3-5), and can provide the scaffold for chiral ligands (6, 7) and valuable organic materials (8). However, traditional isoquinoline syntheses such as the Bischler-Napieralski (9, 10), 12), and Pomeranz-Fritsch reactions (13-15) all centre around the lynchpin of electrophilic aromatic substitution and are thus often limited to electron-rich carbocycles (Scheme 1A). It is also imperative to develop routes to highly-substituted isoquinolines to fully explore this chemical space, for example, for potential pharmaceutical targets. While recent synthetic efforts have greatly expanded the diversity of isoquinoline motifs available (16-29), new routes to isoquinolines are still highly desirable, particularly ones with the ability to directly access the isoquinoline moiety in a range of oxidation levels and which do not require highly-specialized starting materials.Originally reported by Palucki and Buchwald (30), Hamann and Hartwig (31), and Miura and coworkers (32), the palladiumcatalyzed α-arylation of enolates has recently emerged as a powerful new reaction in synthetic organic chemistry (33-35). Key to its success has been the design of appropriate ligands for palladium that have precisely engineered steric and electronic properties to enable the various steps in the catalytic cycle to proceed with maximum efficiency (36-39). The reaction's utility has also been greatly enhanced by the development of robust preformed palladium catalysts. Properties such as air stability and very high reactivity in a range of systems have greatly expanded the potential uses of these catalysts (40-43). However, the α-arylation reaction has seen limited use in the de novo construction of aromatic compounds (44-51) and is still greatly underused in this regard, especially because the bond forming abilities provided by this powerful reaction can greatly simplify the design of routes to heavily-substituted aromatic compounds. Hence, we decided to explore the scope of this new catalytic method in the synthesis of important heteroaromatic ring systems, beginning our investigations with the isoquinoline nucleus. ResultsIn our disconnection approach we envisaged that key pseudo-1,5-dicarbonyl intermediates 3 could be accessed via the palladiumcatalyzed α-arylation of ketones 1 with aryl halides 2 possessing a protected aldehyde or ketone in the ortho-position (52). Subsequent treatment of these inter...

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confidence: 99%

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

Donohoe

Pilgrim

Jones

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Ethyl {11-morpholino -7,8,9,10-tetrahydro [1,2,4] [2,3-c]isoquinolin-2-yl}acetate (7): Compound 5 (0.70 g, 0.002 mol) and diethyl malonate (5 mL) were heated under reflux for 2 h. Then the reaction mixture was allowed to cool. The solid product was filtered off and recrystallised from ethanol to give brown crystals in 68% yield, m.p.…”

Section: Methodsmentioning

confidence: 99%

“…1 Among the members of this class of compounds; tetrahydroisoquinoline derivatives constitute a major group. Many of them exhibit important biological activities, for example, antiinflammatory, anti-microbial, anti-leukaemic, and anti-tumour properties, 2,3 anti-HIV, and other biological activities.…”

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confidence: 99%

Reactions of 1-Amino-5-Morpholino-6,7,8,9-Tetrahydrothieno[2,3-c] Isoquinoline- 2-Carbonitrile

El‐Dean

Radwan

Zaki

2010

Journal of Chemical Research

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1-Amino -5-morpholino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carbonitrile has been converted to the chloroacetylamino derivative which was subjected to nucleophilic substitution reactions with different amines. Reaction of 1-amino-5-morpholino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carbonitrile with triethyl orthoformate followed by cyclisation with hydrazine yielded an aminoiminopyrimidine derivative. The latter was used as a starting material for the synthesis of a variety of fused heterocyclic compounds which include triazolopyrimidothienotetrahydroisoquinolines.

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“…One of the most common oxoaporphine alkaloids is liriodenine, which is found in at least 86 genera and 240 Annonaceae species CAVÉ, 1975CAVÉ, , 1979CAVÉ, , 1983CAVÉ, , 1988CAVÉ, , 1994BENTLEY, 1997BENTLEY, , 2001BENTLEY, , 2002BENTLEY, , 2003BENTLEY, , 2004BENTLEY, , 2005BENTLEY, , 2006GONZÁLEZ-ESQUINCA, 2001;DE LA CRUZ, 2012). This alkaloid is present in members of the Magnoliid clade (Canellales, Piperales, Laurales, and Magnoliales), with many representatives in the Magnoliales (143 Annonaceae and 35 Magnoliaceae species), as well as in phylogenetically distant Angiosperms (Alismatales, Rosales, Sapindales, Malvales, and Gentianales).…”

Section: The Origin Of the Questionsmentioning

confidence: 99%

Alkaloids and acetogenins in Annonaceae development: biological considerations

et al. 2014

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-Chemical studies of the plant family Annonaceae have intensified in the last several decades due to the discovery of annonaceous molecules with medicinal potential (e.g., benzylisoquinoline alkaloids and acetogenins). Approximately 500 alkaloids have been identified in 138 Annonaceae species in 43 genera. In addition, until 2004, 593 annonaceous acetogenins (ACGs) had been identified, from 51 species in 13 genera.This suggests that plants from this family allocate important resources to the biosynthesis of these compounds. Despite the diversity of these molecules, their biological roles, including their physiological and/ or ecological functions, are not well understood. In this study, it was provided new data describing the variety and distribution of certain alkaloids and ACGs in annonaceous plants in distinct stages of development. The potential relationships among some of these compounds and the seasonally climatic changes occurring in the plant habitat are also discussed. These data will improve our understanding of the secondary metabolism of these pharmacologically important molecules and their expression patterns during development, which will help to determine the optimal growth conditions and harvest times for their production. Index terms: early development, secondary metabolism, ecological functions, phenology. ALCALOIDES E ACETOGENINAS NO DESENVOLVIMENTO DE ANNONACEAE: CONSIDERAÇÕES BIOLÓGICASRESUMO -Estudos químicos em plantas da família Annonaceae se intensificaram nas últimas décadas, devido à descoberta de moléculas de anonáceas com potencial medicinal (por exemplo, alcalóides benzilisoquinolina e acetogeninas). Aproximadamente 500 alcaloides têm sido identificados em 138 espécies de Annonaceae em 43 gêneros. Além disso, até 2004, 593 acetogeninas de annonaceas (ACGs) foram identificados, a partir de 51 espécies em 13 gêneros. Isto sugere que as plantas desta família atribuem recursos importantes para a biossíntese destes compostos. Apesar da diversidade destas moléculas, suas funções biológicas, incluindo as suas funções fisiológicas e/ou ecológicas, não são bem compreendidas. Neste estudo, foram fornecidos novos dados que descrevem a variedade e a distribuição de certos alcaloides e ACGs em annonaceas em fases distintas de desenvolvimento. As possíveis relações entre alguns destes compostos e as alterações climáticas sazonais ocorrendo no habitat são também discutidas. Estes dados vão melhorar a nossa compreensão do metabolismo secundário dessas moléculas farmacologicamente importantes e seus padrões de expressão durante o desenvolvimento, o que ajudará a determinar as condições ideais de crescimento e épocas de colheita para a sua produção. Termos para indexação: desenvolvimento inicial, metabolismo secundário, funções ecológicas, fenologia.

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β-Phenylethylamines and the isoquinoline alkaloids

Cited by 154 publications

References 111 publications

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

Reactions of 1-Amino-5-Morpholino-6,7,8,9-Tetrahydrothieno[2,3-c] Isoquinoline- 2-Carbonitrile

Alkaloids and acetogenins in Annonaceae development: biological considerations

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