Biosynthesis of naphthylisoquinoline alkaloids: synthesis and incorporation of an advanced 13C2-labeled isoquinoline precursor

Bringmann, Gerhard; Mutanyatta-Comar, Joan; Greb, Marco; Rüdenauer, Stefan; Noll, Torsten F; Irmer, Andreas

doi:10.1016/j.tet.2006.12.022

Cited by 33 publications

(11 citation statements)

References 22 publications

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“…The plant family Ancistrocladaceae – together with the related Dioncophyllaceae – has been in the focus of our most recent phytochemical investigations 1–4 . This interest is justified by the exclusive occurrence of polyketide-derived naphthylisoquinoline alkaloids in these plants 5–8 . The chemical thrill induced by their broad structural diversity 2,9 , unprecedented biosynthesis, and pronounced biological activities has made them most attractive natural products 10–14 .…”

Section: Introductionmentioning

confidence: 99%

An Unusually Broad Series of Seven Cyclombandakamines, Bridged Dimeric Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ealaensis

Tshitenge

Bruhn

Feineis

et al. 2019

Sci Rep

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A series of seven unusual dimeric naphthylisoquinoline alkaloids was isolated from the leaves of the tropical liana Ancistrocladus ealaensis J. Léonard, named cyclombandakamine A (1), 1- epi -cyclombandakamine A (2), and cyclombandakamines A 3–7 (3–7). These alkaloids have a chemically thrilling structural array consisting of a twisted dihydrofuran-cyclohexenone-isochromene system. The 1′″-epimer of 4, cyclombandakamine A 1 (8), had previously been discovered in an unidentified Ancistrocladus species related to A. ealaensis . Both lianas produce the potential parent precursor, mbandakamine A (9), but only A. ealaensis synthesizes the corresponding cyclized form, along with a broad series of slightly modified analogs. The challenging isolation required, besides multi-dimensional chromatography, the use of a pentafluorophenyl stationary phase. Featuring up to six stereocenters and two types of chiral axes, their structures were elucidated by means of 1D and 2D NMR, HRESIMS, in combination with oxidative chemical degradation experiments as well as chiroptical (electronic circular dichroism spectroscopy) and quantum chemical calculations. Compared to the ‘open-chain’ parent compound 9, these dimers displayed rather moderate antiplasmodial activities.

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Section: Introductionmentioning

confidence: 99%

An Unusually Broad Series of Seven Cyclombandakamines, Bridged Dimeric Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ealaensis

Tshitenge

Bruhn

Feineis

et al. 2019

Sci Rep

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“…Natural isoquinolines are one of the largest groups of alkaloids. Among them, there is a relatively small but important class of iminium moiety-containing isoquinoline alkaloids, such as quaternary benzo[c] phenanthridine alkaloids (QBAs), quaternary N-naphthyl isoquinolines, berberines and so on 1,2) (Fig. 1).…”

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confidence: 99%

Synthesis and <i>in Vitro</i> Antifungal Activities of New 2-Aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium Bromides

Yang

Yao

Qin

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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2-Aryl-3,4-dihydroisoquinolin-2-iums might be considered as a class of simple analogues of natural quaternary benzo[c]phenanthridine alkaloids. In this paper, 26 new 2-aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium bromides with various substituents in N-aromatic ring were synthesized from commercially available 1,3-benzodioxole in good to excellent yields. All the compounds were elucidated by MS, high resolution (HR)-MS, IR, 1 H-and 13 C-NMR analysis, and evaluated for antifungal activities in vitro against Alternaria alternate, Curvularia lunata and Fusarium oxysporum sp. niveum at 50 µg/mL. Most of the compounds showed higher activities against all the test fungi than their natural model compounds sanguinarine and chelerythrine. For A. alternate and Curvularia lunata, most of them were also more active than thiabendazole, a commercial fungicide standard. The structure-activity relationship indicated that the substituent in N-aromatic ring and its position had significant effect on the activity. The general trend was that halogen atoms and CF 3 remarkably enhanced the activity while CH 3 and OCH 3 decreased the activity. Generally, osubstituted isomers were more active than m-and p-substituted isomer. The present results suggest that the title compounds are potential for the development of new isoquinoline antimicrobial agents.Key words 3,4-dihydroisoquinolinium; 1,2,3,4-tetrahydroisoquinoline; N-heterocyclization; antifungal activity; CuCl 2 -catalyzed oxidative coupling reaction; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidation Alkaloids represent a very extensive group of secondary metabolites with diverse structures, distribution in nature, and biological effects. Natural isoquinolines are one of the largest groups of alkaloids. Among them, there is a relatively small but important class of iminium moiety-containing isoquinoline alkaloids, such as quaternary benzo[c] phenanthridine alkaloids (QBAs), quaternary N-naphthyl isoquinolines, berberines and so on 1,2) (Fig. 1). In the past decades, these compounds have aroused interests of both chemists and pharmacologists for their chemical reactivity and extensive bioactivities including antitumor, [3][4][5] antimicrobial, [6][7][8][9][10][11][12] anti-inflammation, 13) antiplatelet aggregation, 14) anti-angiogenesis, 15) anti-acetylcholinesterase, 16) and antiparasite activities. [17][18][19][20] Our previous studies demonstrated that sanguinarine and chelerythrine ( Fig. 1) might serve as ideal lead compounds to develop new isoquinoline antimicrobial and acaricidal agents. Meanwhile, the iminium moiety (C= N + ) was their determinant for their bioactivities. 11,12,17) The similar cases were also found for antitumor activity of 7-demethyl chelerythrine (NK109) 21) and antibacterial activity of berberine.9) In addition, the molecular planarity was also proven to be an important factor for the activity.21) Based on understanding of the structure-activity relationship above and the aim of developing more potent QBAs-like drugs, we intended to design a cl...

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“…Naphthylisoquinoline alkaloids are structurally, biosynthetically, and pharmacologically unique secondary metabolites, isolated from lianas belonging to the paleotropic plant families Ancistrocladaceae and Dioncophyllaceae . They consist of a naphthalene and an isoquinoline portion, both derived from polyketide precursors,, linked together by a biaryl axis that is, in most cases, rotationally hindered and, thus, stereogenic. Depending on their individual structures, they have pronounced anti‐infective or antitumoral activities ,.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Total Synthesis of Mbandakamine A and Further Antiplasmodial Naphthylisoquinoline Dimers

et al. 2018

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The first total synthesis of mbandakamine A, an unsymmetrically coupled dimeric naphthylisoquinoline alkaloid with a high steric hindrance, is described. Key step was the phenol‐oxidative cross‐coupling of its two 5,8’‐linked monomeric units, 5‐epi‐korupensamine E and 8‐O‐methylkorupensamine A. These two naphthylisoquinolines were synthesized atroposelectively by applying the ′lactone method′. As an alternative to the largely separate synthesis of the two monomers, both of them were provided simultaneously, by the – intentionally non‐selective – O‐demethylation of a late joint precursor, thus shortening the synthesis substantially. Oxidative coupling of a 1:1 mixture of the two monomers provided mbandakamine A as a single atropisomer, along with four further naphthylisoquinoline dimers, nearly all of them based on new coupling types. Some of these new quateraryls showed excellent antiplasmodial activities, in particular the 6’‐6’’‐coupled main product.

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Biosynthesis of naphthylisoquinoline alkaloids: synthesis and incorporation of an advanced 13C2-labeled isoquinoline precursor

Cited by 33 publications

References 22 publications

An Unusually Broad Series of Seven Cyclombandakamines, Bridged Dimeric Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ealaensis

An Unusually Broad Series of Seven Cyclombandakamines, Bridged Dimeric Naphthylisoquinoline Alkaloids from the Congolese Liana Ancistrocladus ealaensis

Synthesis and <i>in Vitro</i> Antifungal Activities of New 2-Aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium Bromides

Biomimetic Total Synthesis of Mbandakamine A and Further Antiplasmodial Naphthylisoquinoline Dimers

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