DNA cleavage by acyclic eneyne-allene systems related to neocarzinostatin and esperamicin-calicheamicin

Nagata, Ryu; Yamanaka, Hideo; Murahashi, Eiji; Saito, Isao

doi:10.1016/0040-4039(90)80181-k

Cited by 123 publications

(42 citation statements)

References 17 publications

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“…The Bergman cyclization plays a major role in enediyne antibiotics, whose mode of action involves the formation of substituted variants of biradical 6 a and their ability to abstract hydrogen atoms from the DNA sugar phosphate backbone in cancer cells . This is similarly true for anticancer antibiotics based on the Myers–Saito cyclization of eneyneallenes . The parent structure of this compound class 5 b can either cyclize in a C1‐C6 fashion to yield biradical 6 c (reaction R3c) or in a C2‐C6 fashion (also called the Schmittel cyclization) to afford biradical 6 d (reaction R3d).…”

Section: Thermochemical Aspects Of Mirf Reactionsmentioning

confidence: 87%

“…[23] This is similarly true for anticancer antibiotics based on the Myers-Saito cyclization of eneyneallenes. [24,25] Thep arent structure of this compound class 5b can either cyclize in aC 1-C6 fashion to yield biradical 6c (reaction R3c) or in aC 2-C6 fashion (also called the Schmittel cyclization) [26] to afford biradical 6d (reaction R3d). This latter cyclization is particularly relevant in terminally substituted derivatives of 5b.…”

Section: Thermochemical Aspects Of Mirf Reactionsmentioning

confidence: 99%

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Molecule‐Induced Radical Formation (MIRF) Reactions—A Reappraisal

2020

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Radical chain reactions are commonly initiated through the thermal or photochemical activation of purpose‐built initiators, through photochemical activation of substrates, or through well‐designed redox processes. Where radicals come from in the absence of these initiation strategies is much less obvious and are often assumed to derive from unknown impurities. In this situation, molecule‐induced radical formation (MIRF) reactions should be considered as well‐defined alternative initiation modes. In the most general definition of MIRF reactions, two closed‐shell molecules react to give a radical pair or biradical. The exact nature of this transformation depends on the σ‐ or π‐bonds involved in the MIRF process, and this Minireview specifically focuses on reactions that transform two σ‐bonds into two radicals and a closed‐shell product molecule.

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Section: Thermochemical Aspects Of Mirf Reactionsmentioning

confidence: 87%

Section: Thermochemical Aspects Of Mirf Reactionsmentioning

confidence: 99%

Molecule‐Induced Radical Formation (MIRF) Reactions—A Reappraisal

2020

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“…Die Bergman‐Cyclisierung spielt eine herausragende Rolle im Wirkmechanismus von Endiin‐Antibiotika, in dem substituierte Varianten des Diradikals 6 a für Wasserstoffabstraktions‐Reaktionen vom Zucker‐Phosphat‐Rückgrat der DNA von Krebszellen verantwortlich sind . Dies trifft ebenfalls auf Antikrebsmittel zu, die auf der Myers‐Saito‐Cyclisierung von Eninallenen basieren . Die Grundstruktur dieser Verbindungsklasse 5 b kann entweder durch C1‐C6‐Cyclisierung zu Diradikal 6 c (Reaktion R3c) führen oder nach C2‐C6‐Cyclisierung (die auch als Schmittel‐Cyclisierung bekannt ist) das Diradikal 6 d (Reaktion R3d) ergeben.…”

Section: Thermodynamische Aspekte Von Mirf‐reaktionenunclassified

“…[23] Dies trifft ebenfalls auf Antikrebsmittel zu, die auf der Myers-Saito-Cyclisierung von Eninallenen basieren. [24,25] Die Grundstruktur dieser Verbindungsklasse 5b kann entweder durch C1-C6-Cyclisierung zu Diradikal 6c (Reaktion R3c) führen oder nach C2-C6-Cyclisierung (die auch als Schmittel-Cyclisierung bekannt ist) [26] [31] Kombination dieser Daten mit aktuellen Bindungsdissoziationsenergien fürF luorwasserstoff [15] und fürd ie C(9)-H-Bindung in 9,10-Dihydroanthracen (14) [28] [28] oder auf G3B3-Niveau [30] berechneten thermochemischen Daten und liegt deutlich hçher als die Reaktionsenthalpie von DH 298 (R7) =+37.7 kJ mol À1 ,d ie in Lit. [32] [38][39][40] Wird ein ausreichend guter H-Atomdonor wie 14 eingesetzt, ist sogar die Spaltung von N-O-Bindungen wie in N-Hydroxyanilin (33)m çglich (Tabelle 1, Reaktion R12).…”

Section: Thermodynamische Aspekte Von Mirf-reaktionenunclassified

Molekül‐induzierte Radikalbildung – eine Neubewertung

2020

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Radikalkettenreaktionen werden normalerweise durch die thermische oder photochemische Aktivierung von Radikalinitiatoren, durch die photochemische Aktivierung der Substrate selbst oder durch gezielte Redoxprozesse eingeleitet. Woher Radikale in der Abwesenheit dieser Initiierungsstrategien kommen, ist oft wenig bekannt und wird daher auf das Vorhandensein unbekannter Verunreinigungen zurückgeführt. In dieser Situation bieten sich Molekül‐induzierte Radikalbildungs (MIRF)‐Reaktionen als wohldefinierte alternative Initiierungsmechanismen an. In ihrer allgemeinsten Definition reagieren in MIRF‐Reaktionen zwei geschlossenschalige Moleküle unter Bildung eines Radikalpaars oder Diradikals. Der genaue Charakter dieses Prozesses hängt von den σ‐ oder π‐Bindungen ab, die an der MIRF‐Reaktion beteiligt sind, und dieser Kurzaufsatz konzentriert sich besonders auf Reaktionen, in denen zwei σ‐Bindungen in zwei Radikale und ein geschlossenschaliges Produkt umgewandelt werden.

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“…They also reported the catalytic version of that transformation in the presence of 5 mol% of [RhCl(CO) 2 ] 2 at 90°C to furnish 4a in 62% yield along with the by-production of 2-methylnaphthalene (5), the latter of which should be arisen from the MyersSaito cycloaromatization [21][22][23][24][25] of 3a. We have independently reported that treatment of 3-(2-ethynylphenyl) prop-2-ynyl benzenesulfinate (6) with 2.5 mol% of [RhCl(CO) 2 ] 2 at 40°C in an atmosphere of CO effected the successive 2,3-sigmatropic rearrangement and carbonylative [2+2+1] ring-closing reaction of the resulting allenyne species 3b to afford the 8-(phenylsulfonyl)-1H-cyclopent[a] inden-2-one (4b) in a high yield.…”

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confidence: 99%

Synthesis of a Carbon Analogue of Scytonemin

Mukai

Arima

Hirata

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The synthesis of a carbon analogue of scytonemin was accomplished on the basis of molybdenummediated intramolecular double Pauson-Khand type reaction of bis(allenyne), followed by the double aldol condensation of the formed double Pauson-Khand type adduct.Key words scytonemin; allene; [2+2+1] cycloaddition; alkyne; molybdenum; aldol condensation Scytonemin (1) is the cyanobacterial dimeric alkaloid pigment, whose chemical structure has been elucidated by Gerwick and co-workers in 1993, 1) over 100 years after its discovery. Scytonemin has an intriguing novel structural feature, which consists of a two 1,1′-linked cyclopent [b] indole-2(1H)-one framework possessing 4-hydroxybenzylidenes at the 3-positions of the fused tricyclic systems. The biosynthetic studies of scytonemin have been recently made by Walsh and Balskus.2,3) In 2011, Mårtensson and colleagues achieved the first total synthesis of scytonemin by taking advantage of the tandem Heck carbocyclization/Suzuki-Miyaura coupling and a bioinspired oxidative dimerization. 4) Of particular interest is its interesting biological features. Scytonemin is a UVabsorbing pigment that protects important cellular components in a cyanobacteria against harmful UV radiation. [5][6][7][8] Besides this important function, scytonemin exhibits a biological activity as a small molecule inhibitor of polo-like kinase 1 9) and possesses anti-inflammatory and antiproliferative properties. 10)During our studies on the syntheses of various kind of alkaloids, [11][12][13][14][15][16][17][18][19] we became very interested in the highly conjugated and characteristic dimeric structure of scytonemin as well as its biological activity. We postulated that the origin of the biological activity of scytonemin (1) might be elucidated by comparison with its carbon analogue, in which two nitrogen atoms are replaced by two carbon atoms. Therefore, our endeavor was directed toward the synthesis of 2, a carbon analogue of scytonemin (1) (Chart 1).In 2005, Liu and Datta developed the efficient synthesis of 1H-cyclopent[a] inden-2-one (4a) from 1-ethynyl-2-(1,2-propadienyl) benzene (3a) through the Mo(CO) 3 (MeCN) 3 -mediated carbonylative [2+2+1] ring-closing reaction at 25°C in a stoichiometric manner 20) (Chart 2). They also reported the catalytic version of that transformation in the presence of 5 mol% of [RhCl(CO) 2 ] 2 at 90°C to furnish 4a in 62% yield along with the by-production of 2-methylnaphthalene (5), the latter of which should be arisen from the MyersSaito cycloaromatization 21-25) of 3a. We have independently reported that treatment of 3-(2-ethynylphenyl) prop-2-ynyl benzenesulfinate (6) with 2.5 mol% of [RhCl(CO) 2 ] 2 at 40°C in an atmosphere of CO effected the successive 2,3-sigmatropic rearrangement and carbonylative [2+2+1] ring-closing reaction of the resulting allenyne species 3b to afford the 8-(phenylsulfonyl)-1H-cyclopent[a] inden-2-one (4b) in a high yield.26) In this case, the formation of 2-methylnaphthalene could not be detected in the reaction mixture. We now report t...

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DNA cleavage by acyclic eneyne-allene systems related to neocarzinostatin and esperamicin-calicheamicin

Cited by 123 publications

References 17 publications

Molecule‐Induced Radical Formation (MIRF) Reactions—A Reappraisal

Molecule‐Induced Radical Formation (MIRF) Reactions—A Reappraisal

Molekül‐induzierte Radikalbildung – eine Neubewertung

Synthesis of a Carbon Analogue of Scytonemin

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