Electronic effects in the thermal C2–C6 biradical cyclisation of enyne-allenes

Schmittel, Michael; Maywald, Michael

doi:10.1039/b007811p

Cited by 27 publications

(11 citation statements)

References 30 publications

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“…The intermediacy of a diradical in the thermal C 2 –C 6 cyclization of enyne–allenes was further corroborated experimentally by the results of an investigation on electronic effects by varying the substituent R at the alkyne terminus from electron‐withdrawing to electron‐donating groups (NO 2 , CN, F, Me, and OMe) . In differential scanning calorimetry (DSC) kinetic studies, the NO 2 ‐substituted enyne–allene showed the lowest cyclization temperature, whereas the fluoro‐substituted one held the highest onset temperature.…”

Section: Experimental Evidence For the C2–c6 Diradicalmentioning

confidence: 74%

The thermal C²–C⁶ (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

Schmittel

Vavilala

Çınar

2011

J of Physical Organic Chem

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The thermal C 2 -C 6 /ene cyclization of enyne-allenes has become an exciting venue for both mechanistic and synthetic studies. While at first most efforts were aimed at establishing the diradical nature of the thermal process and to derive therefrom efficient protocols for synthetic schemes, recent evidence has disclosed the C 2 -C 6 cyclization as a unique reaction heavily influenced by nonstatistical dynamic effects. Depending on the substituents at the enyne-allene, one can readily identify transitions between classical and nonstatistical behaviors on the basis of experimental data. We are grateful to him for his friendship and many scientific enlightenments.a M. Schmittel, C. Vavilala, M. E. Cinar FB 8 (

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Section: Experimental Evidence For the C2–c6 Diradicalmentioning

confidence: 74%

The thermal C²–C⁶ (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

Schmittel

Vavilala

Çınar

2011

J of Physical Organic Chem

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“…[1][2][3] Neocarzinostatin (NCS), which was the first naturally occurring enediyne chromoprotein studied, [4,5] displays an interesting feature; its carrier protein is able to divert the enediyne cycloaromatization into a distinct pathway. How the protein directs the irreversible chemistry of its bound enediyne has remained a profound mystery.…”

Section: Introductionmentioning

confidence: 99%

Role of Steric Effects in Protein‐Directed Enediyne Cycloaromatization of Neocarzinostatin

Chi

Chien

Liu

et al. 2010

Chemistry A European J

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The antibiotic neocarzinostatin comprises a carrier protein with a well-defined cavity for accommodating an active enediyne chromophore. The protein has two disulfides, one (Cys(37)-Cys(47)) lies on the cavity bottom and the other (Cys(88)-Cys(93)) in a constrained short loop. When the chromophore is not bound to the protein, a thiol-induced cycloaromatization of the enediyne into a tetrahydroindacene derivative is responsible for the potent antitumor activity. When it is protein-bound, the protein diverts the cycloaromatization pathway to form a distinct hydroxyisochromene-type product. How the protein directs the enediyne chemistry is an interesting puzzle, and various suggestions have been proposed in the past. We screened more than fifty thiols and manipulated conditions to locate reaction features and search for factors that could influence the protein directing strength. Thiol- and oxygen-concentration-dependence studies suggested that disulfides, which maintain the steric rigidity of the protein, could play a key role in diverting the cycloaromatization pathway. For direct proofs, we made mutations at each of the two disulfides by replacing sulfur atoms with oxygen. Circular dichroism and two-dimensional NMR spectroscopy studies suggested that the mutations changed neither the protein conformation nor the ligand interactions. Analyses of the thiol-induced cycloaromatization revealed that rupture of Cys(37)-Cys(47) made the protein almost completely lose its chemical directing ability, whereas rupture of Cys(88)-Cys(93) had only a minor influence. The results demonstrated that the steric rigidity of the binding cavity, but not necessary the whole protein, played an important role in the protein-directed mechanism.

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“…f Auch durch Substitution mit Phenylgruppen lässt sich die Energetik umkehren (benzylische Stabilisierung im Übergangszustand der Schmittel‐Cyclisierung) 138a. b Substituierte Phenylgruppen in den Acetylenpositionen zeigen keinen systematischen Einfluss auf die Barriere der Schmittel‐Reaktion (die jedoch stets günstiger zu bleiben scheint als die C2‐C7‐Cyclisierung) 140…”

Section: Para‐didehydroaromaten Und Die Bergman‐cyclisierungunclassified

100 Jahre Didehydroaromaten

2003

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Electronic effects in the thermal C2–C6 biradical cyclisation of enyne-allenes

Cited by 27 publications

References 30 publications

The thermal C²–C⁶ (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

The thermal C²–C⁶ (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

Role of Steric Effects in Protein‐Directed Enediyne Cycloaromatization of Neocarzinostatin

100 Jahre Didehydroaromaten

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Electronic effects in the thermal C2–C6 biradical cyclisation of enyne-allenes

Cited by 27 publications

References 30 publications

The thermal C2–C6 (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

The thermal C2–C6 (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

Role of Steric Effects in Protein‐Directed Enediyne Cycloaromatization of Neocarzinostatin

100 Jahre Didehydroaromaten

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The thermal C²–C⁶ (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics

The thermal C²–C⁶ (Schmittel)/ene cyclization of enyne–allenes – crossing the boundary between classical and nonstatistical kinetics