Browsing by Author "Popik V V"

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Photochemical Generation and Reversible Cycloaromatization of a 9-Membered Ring Cyclic Enediyne
(The Southeast Regional Meeting of the American Chemical Society (SERMACS), Nashville, TN, USA, 2008) Pandithavidana D R; Popik V V
The extreme cytotoxicity of natural enediyne antibiotics is attributed to the ability of the (Z)-3-ene-1,5-diyne fragment incorporated into a 10- or 9-membered ring cyclic system to undergo Bergman cyclization and producing dDNA-damaging p-benzyne diradical. The rate of this reaction strongly depends on the ring size. Thus 11-membered ring enediynes are stable, 10-membered ring analogs undergo slow cycloaromatization under ambient conditions or mild heating. Very little is known about reactivity of 9-membered ring enediynes due to their instability. We have developed a thermally stable photo-precursor of 1 of 9-membered enediyne 2, in which one of the triple bonds is replaced by the cyclopropenone group. UV irradiation of 1 results in the efficient decarbonylation (?254 = 0.34) and the formation of reactive enediyne 2. The latter undergoes clean cycloaromatization to 2,3-dihydro-1H-cyclopenta[b]naphthalen-1-ol (4) with ca. 2 h a life-time in isopropanol at 25 �C. The rate of this reaction depends linearly on the concentration of hydrogen donor and shows primary kinetic isotope effect in 2-propanol-d8. These observations, along with high negative entropy of activation, indicate that enediyne 2 exists in a rapid equilibrium with p-benzyne diradical 3. The rate-limiting step of the cycloaromatization reaction is hydrogen abstraction by the diradical 3. Synthesis of cyclopropenone 1 and DNA-clevaging activity of the photo-generated enediyne 2 will be also discussed.
Photochemical Generation and Reversible Cycloaromatization of a Nine-Membered Ring Cyclic Enediyne
(Journal of the American Chemical Society, 2009) Pandithavidana D R; Poloukhtine A; Popik V V
Irradiation of the nine-membered ring enediyne precursor, which has one of its triple bonds masked as cyclopropenone, efficiently (? = 0.34) generates the reactive 4,5-benzocyclonona-2,6-diynol. The latter rapidly equilibrates with the corresponding 1,4-didehydronaphthalene diradical and then undergoes rate-limiting hydrogen abstraction to produce the ultimate product of the Bergman cyclization, benz[f]indanol.
Photochemical Triggering of the Bergman and Myers?Saito Cyclizations
(Australian Journal of Chemistry, 2010) Pandithavidana D R; Kuzmin A; Popik V V
Two strategies for the photochemical generation of reactive enediyne compounds and their subsequent cycloaromatization to p-benzyne or ?,3-didehydrotoluene derivatives are discussed in this account. The first method employs a photo-Wolff reaction of stable 11- or 12-membered ring precursor enediynes containing the 2-diazo-1,3-diketone moiety. Irradiation of these compounds results in ring contraction and the formation of two isomeric enediynes possessing an enolized ?-ketoester fragment. One of the isomers undergoes the conventional Bergman cyclization, whereas the other isomerizes into the enyne-allene tautomer, which rapidly cyclizes via a Myers?Saito mechanism. The second strategy consists of replacing the triple bond in a cyclic enediyne or enyne-allene structure with a cyclopropenone group, rendering them thermally stable. Photolysis of cyclopropenones results in efficient decarbonylation and the regeneration of a triple bond, restoring the enediyne ?-system. The generation of reactive enediynes by non-resonant two-photon excitation using wavelengths within a ?phototherapeutic window? was also demonstrated. Photogenerated enediynes show significant nuclease activity, efficiently inducing single-strand dDNA cleavage.