2566-57-6Relevant academic research and scientific papers
Parallel and competitive pathways for substrate desaturation, hydroxylation, and radical rearrangement by the non-heme diiron hydroxylase AlkB
Cooper, Harriet L. R.,Mishra, Girish,Huang, Xiongyi,Pender-Cudlip, Marilla,Austin, Rachel N.,Shanklin, John,Groves, John T.
, p. 20365 - 20375 (2013/02/25)
A purified and highly active form of the non-heme diiron hydroxylase AlkB was investigated using the diagnostic probe substrate norcarane. The reaction afforded C2 (26%) and C3 (43%) hydroxylation and desaturation products (31%). Initial C-H cleavage at C2 led to 7% C2 hydroxylation and 19% 3-hydroxymethylcyclohexene, a rearrangement product characteristic of a radical rearrangement pathway. A deuterated substrate analogue, 3,3,4,4-norcarane-d 4, afforded drastically reduced amounts of C3 alcohol (8%) and desaturation products (5%), while the radical rearranged alcohol was now the major product (65%). This change in product ratios indicates a large kinetic hydrogen isotope effect of ～20 for both the C-H hydroxylation at C3 and the desaturation pathway, with all of the desaturation originating via hydrogen abstraction at C3 and not C2. The data indicate that AlkB reacts with norcarane via initial C-H hydrogen abstraction from C2 or C3 and that the three pathways, C3 hydroxylation, C3 desaturation, and C2 hydroxylation/radical rearrangement, are parallel and competitive. Thus, the incipient radical at C3 either reacts with the iron-oxo center to form an alcohol or proceeds along the desaturation pathway via a second H-abstraction to afford both 2-norcarene and 3-norcarene. Subsequent reactions of these norcarenes lead to detectable amounts of hydroxylation products and toluene. By contrast, the 2-norcaranyl radical intermediate leads to C2 hydroxylation and the diagnostic radical rearrangement, but this radical apparently does not afford desaturation products. The results indicate that C-H hydroxylation and desaturation follow analogous stepwise reaction channels via carbon radicals that diverge at the product-forming step.
Desaturase reactions complicate the use of norcarane as a mechanistic probe. Unraveling the mixture of twenty-plus products formed in enzyme-catalyzed oxidations of norcarane
Newcomb, Martin,Chandrasena, R. Esala P.,Lansakara-P, Dharmika S. P.,Kim, Hye-Yeong,Lippard, Stephen J.,Beauvais, Laurance G.,Murray, Leslie J.,Izzo, Viviana,Hollenberg, Paul F.,Coon, Minor J.
, p. 1121 - 1127 (2007/10/03)
(Chemical Equation Presented) Norcarane, bicyclo[4.1.0]heptane, has been widely used as a mechanistic probe in studies of oxidations catalyzed by several iron-containing enzymes. We report here that, in addition to oxygenated products, norcarane is also oxidized by iron-containing enzymes in desaturase reactions that give 2-norcarene and 3-norcarene. Furthermore, secondary products from further oxidation reactions of the norcarenes are produced in yields that are comparable to those of the minor products from oxidation of the norcarane. We studied oxidations catalyzed by a representative spectrum of iron-containing enzymes including four cytochrome P450 enzymes, CYP2B1, CYPΔ2B4, CYPΔ2E1, and CYPΔ2E1 T303A, and three diiron enzymes, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), toluene monooxygenase (ToMO) from Pseudomonas stutzeri OX1, and phenol hydroxylase (PH) from Pseudomonas stutzeri OX1. 2-Norcarene and 3-norcarene and their oxidation products were found in all reaction mixtures, accounting for up to half of the oxidation products in some cases. In total, more than 20 oxidation products were identified from the enzyme-catalyzed reactions of norcarane. The putative radical-derived product from the oxidation of norcarane, 3- hydroxymethylcyclohexene (21), and the putative cation-derived product from the oxidation of norcarane, cyclohept-3-enol (22), coelute with other oxidation products on low-polarity GC columns. The yields of product 21 found in this study are smaller than those previously reported for the same or similar enzymes in studies where the products from norcarene oxidations were ignored, and therefore, the limiting values for lifetimes of radical intermediates produced in the enzyme-catalyzed oxidation reactions are shorter than those previously reported.
185-nm Photolysis and Pyrolysis of the Spirocyclopropane-Substituted Azoalkanes of 2,3-Diazatricyclo4,9>non-2-ene and Their Denitrogenated Hydrocarbon Products, the Tricyclo2,7>heptanes
Adam, Waldemar,Zang, Gerald
, p. 3315 - 3323 (2007/10/02)
The 185-nm photolysis and pyrolysis of the spirocyclopropane derivatives of the azoalkanes 2,3-diazatricyclo4,9>non-2-ene (1a), 4',5'-diazaspiro(cyclopropane-1,8'-tricyclo3,7>non-4'-ene) (1b), and 4',5'-diazadispiro(cyclopropane-1,2'-tricyclo3,7>non-4'-ene-8',1''-cyclopropane) (1c) and their denitrogenated hydrocarbon derivatives tricyclo2,7>heptane (2a), spiro(cyclopropane-1,3'-tricyclo2,7>heptane (2b), and dispiro(cyclopropane-1,3'-tricyclo2,7>heptane-6',1''-cyclopropane) (2c) were investigated.It was shownthat the 185-nm photochemical behavior of these substrates does not depend on the degree of spirocyclopropane substitution.As common products in the 185-nm photolysis of the azoalkanes 1a-c were obtained the tricycloalkanes 2a-c (major products), the norbornenes 3a-c, the vinylcyclopentenes 5a-c (minor products), and the exo-methylenecyclohexenes 6a-c (traces).In the case of the parent azoalkane 1a additionally bicyclohept-2-ene (4) and bicyclohept-2-ene (7a) were detected.The major products in the photolysis of the tricycloheptanes 2a-c were the vinylcyclopentenes 5a-c, but also the norbornenes 3a-c and the methylenecyclohexenes 6a-c were formed in considerable amounts.Although the norbornenes 3a-c and the bicycloheptene 4a are logical Wagner-Meerwein rearrangement products, attempts to trap the suspected radical-cationic and zwitterionic intermediates with CF3CH2OH failed.Efforts to generate the authentic radical-cationic species by means of photosensitized elctron transfer (PET) by using sensitizers such as cyanoarenes, quinones, and pyrylium salts were unproductive.Vibrationally excited bicyclohepta-2,7-diyls, generated by the pyrolyses of 2a-c, are not precursors to the norbornenes 3a-c because, instead of such rearrangement products, cyclobutane cleavage of the bicyclopentane moiety takes place to afford the isomeric vinylcyclopentenes 5'a-c.Carbene intermediates, produced either from the 1,3-diyl-type species through fragmentation or from the photodenitrogenation of diazoalkanes, which are generated by retro-cleavage of n,?* excited azoalkanes 1a-c, in turn obtained through internal conversion of higher excited states such as 1?,?*, 1n,?*, and Ry, are proposed as the most likely precursors to either the vinylcyclopentenes 5a-c or methylenecyclohexenes 6a-c, respectively.In violation of Kasha's rule, photochemistry directly from the higher states of the azoalkanes 1a-c competes with internal conversion to the lowest excited state, namely the n,?* state, as it was shown by the formation of norbornenes 3a-c.
REACTIONS OF DIAZOALKANES WITH UNSATURATED COMPOUNDS. 6. CATALYTIC CYCLOPROPANATION OF UNSATURATED HYDROCARBONS AND THEIR DERIVATIVES WITH DIAZOMETHANE
Dzhemilev, U. M.,Dokichev, V. A.,Sultanov, S. Z.,Khusnutdinov, R. I.,Tomilov, Yu. V.,et al.
, p. 1707 - 1714 (2007/10/02)
A systematic study has been conducted of the catalytic reaction of diazomethane with cyclic and polycyclic unsaturated hydrocarbons, conjugated dienes, as well as with a series of functionalized unsaturated conpounds.The feasibility of using transition metal, nontransition metal, and rare earth metal compounds of, for example, Co, Ni, Zr, Rh, and Dy, has been demonstrated for the first time.It has also been established that Pd(acac)2 has very high activity as a catalyst for the cyclopropanation of terminal and endocyclic double bonds by diazomethane, and that its activity is reduced upon the introduction of n-donor ligands or in the presence of strong polar solvents.
PHOTOLYSIS OF THE AZOALKANE 2,3-DIAZATRICYCLO4,9>NON-2-ENE: DIRECT OBSERVATION OF 4-CYCLOHEXENYLDIAZOMETHANE
Adam, Waldemar,Carballeira, Nestor,Gillaspey, William D.
, p. 5473 - 5476 (2007/10/02)
Besides denitrogenation to the tricycloalkane 8, the photolysis of azoalkane 3 affords the diazoalkane 4, which serves as precursor to the minor hydrocarbon products 9, 10 and 11; irradiation of azoalkane 3 with the 333.6 nm line of an 18-W argon ion laser was essential to obtain preparative quantities of diazoalkane 4 for its detection and identification.
Organic Photochemistry in the Far-ultraviolet: Unusual Wavelength Dependence in Solution-phase Irradiations
Srinivasan, Ra,Baum, Thomas,Brown, Karen,Ors, Jose,White, Lloyd S.,et al.
, p. 973 - 974 (2007/10/02)
In the region from 185 to 215 nm certain compounds show extreme selectivity in their photodecomposition modes in solution depending on the wavelength even though such compounds possess only one intense absorption in this region.
