13161-30-3Relevant articles and documents
Pattern of Addition of Hydroxyl Radicals to the Spin Traps α-Pyridyl 1-Oxide N-tert-Butyl Nitrone
Neta, P.,Steenken, S.,Janzen, Edward G.,Shetty, Raghav V.
, p. 532 - 534 (1980)
Hydroxyl radicals react with α-2, α-3, and α-4-pyridyl 1-oxide N-tert-butyl nitrones (POBN) with rate constants of 3.2E9, 4.8E9, and 3.5E9 M-1 s-1, respectively, via addition to two distinct sites.Addition to the pyridine ring yields short-lived radicals of the hydroxyazacyclohexadienyl type, while addition to the nitrone function in the side chain yields long-lived nitroxide radicals.The distribution of OH addition at the two molecular sites was determined by using differences in reducing power upon reaction of the different types of radicals with IrCl62-.The fraction of OH attack on the pyridine ring is ca. 0.6, relatively independent of the isomeric structure of the POBN.
Alkyl transfer with retention and inversion of configuration: Reexamination of a putative [1s,4s] sigmatropic rearrangement
Wolfe, Saul,Yang, Kiyull,Weinberg, Noham,Shi, Zheng,Hsieh, Yih-Huang,Sharma, Rajendra Dev,Ro, Stephen,Kim, Chan-Kyung
, p. 886 - 902 (1998)
The thermal rearrangement of 2-alkoxypyridine-1-oxides to 1-alkoxy-2-pyridones, which has been reported to proceed by an intramolecular [1s,4s] sigmatropic migration of the alkyl group with retention of configuration and first-order kinetics, has been reexamined. The intramolecular barriers have been computed to be at least 20 kcal mol-1 higher than the reported experimental barriers. An alternative bimolecular mechanism, discovered computationally, has been confirmed by a variety of experiments including crossover studies, determination of solvent effects and secondary H/D isotope effects, and new kinetic and stereochemical studies. In the new mechanism there is an initial intermolecular transfer of the alkyl group, with inversion of configuration, to the N-oxide. Depending on the nature of the alkyl group and the solvent, this is followed by a second transfer, also with inversion of configuration, of one of the alkyl groups of the cationic intermediate to one of the oxygens of the anionic intermediate. The product is then formed either without crossover, by a double inversion of one alkyl group, or with crossover by two single inversions of different alkyl groups. The proposed intermediates of this mechanism can be synthesized; they react to form a 1-alkoxy-2-pyridone at room temperature.
Activation of sulfonate ester based matrix metalloproteinase proinhibitors by hydrogen peroxide
Daniel, Kevin B.,Major Jourden, Jody L.,Negoescu, Kimberly E.,Cohen, Seth M.
body text, p. 313 - 323 (2012/01/13)
This study details the development of matrix metalloproteinase inhibitor prodrugs (proMMPi) that are activated in the presence of reactive-oxygen species (ROS). Conventional matrix metalloproteinase inhibitors (MMPi) utilize a zinc-binding group (ZBG) that chelates to the catalytic zinc(II) ion of matrix metalloproteinases (MMPs) to inhibit their activity. To create ROS-sensitive prodrugs, sulfonate esters were used as a protecting group for the ZBG to block their metal binding ability. Surprisingly, these sulfonate esters were found to be cleaved by H2O2 only when the ZBG contained an N-oxide donor atom moiety. Sulfonate ester derivatives of full-length MMPi based on these ROS-triggerable systems were synthesized. It was found that proMMPi with sulfonate ester protecting groups showed relatively high rates of cleavage in the presence of H2O2 to release the active MMPi. In vitro MMP inhibition studies confirmed a significant increase in inhibitory activity of proMMPi upon addition of H2O2, demonstrating the use of sulfonate esters to act as cleavable triggers for ROS-activated prodrugs.
An efficient synthesis of heterocyclic N-oxides over molecular sieve catalyst
Prasad, M. Ramakrishna,Kamalakar, G.,Madhavi, G.,Kulkarni, S. J.,Raghavan, K. V.
, p. 1577 - 1578 (2007/10/03)
Heterocyclic N-oxides have been synthesized in very high yields over redox molecular sieve catalysts in the presence of H2O2.
