319457-53-9Relevant academic research and scientific papers
Elucidation of the catalytic mechanisms of the non-haem iron-dependent catechol dioxygenases: Synthesis of carba-analogues for hydroperoxide reaction intermediates
Winfield, Christopher J.,Al-Mahrizy, Zeyana,Gravestock, Michael,Bugg, Timothy D.H.
, p. 3277 - 3289 (2007/10/03)
The catalytic mechanisms of the non-haem iron-dependent intradiol and extradiol catechol dioxygenases are thought to involve transient hydroperoxide reaction intermediates, formed by reaction of a catechol substrate with dioxygen. The synthesis of carba-analogues of these intermediates is described in which the hydroperoxide functional group (-OOH) is replaced by a hydroxymethyl group (-CH2OH), and the cyclohexadienone skeleton simplified to a cyclohexanone. Analogues of the "proximal" hydroperoxide in which the hydroxymethyl group was positioned axially with respect to the ring were found to act as reversible competitive inhibitors (Ki 0.7-7.6 mM) for the extradiol enzyme 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB) from Escherichia coli, whereas analogues in which the hydroxymethyl group was positioned equatorially showed no inhibition. In contrast, assays versus the intradiol-cleaving protocatechuate 3,4-dioxygenase from Pseudomonas sp. showed inhibition only by an analogue containing an equatorial hydroxymethyl group (IC50 9.5 mM). These data support the existence of a proximal hydroperoxide intermediate in the extradiol catechol dioxygenase mechanism, and suggest that the conformation adopted by the hydroperoxide reaction intermediate may be an important determinant in the reaction specificity of the extradiol and intradiol dioxygenases. The Royal Society of Chemistry 2000.
Ring-fused and spiro cyclopentenones by Ni(CO)4-promoted intermolecular carbonylative cycloaddition of acetylenes with 3-halo- and 1-(halomethyl)cycloalkenes
Pagès, Lluís,Llebaria, Amadeu,Camps, Francisco,Molins, Elies,Miravitlles, Caries,Moretó, Josep M.
, p. 10449 - 10461 (2007/10/02)
The title carbonylative cycloaddition of five- to eight-member ring 3-halo- and 1-(halomethyl)cycloalkenes with different acetylenes was studied. From moderate to good yields of ring-fused and spiro cyclopentenone derivatives were obtained, especially in the reaction with acetylenes bearing electron-withdrawing substituents by proper selection of the reaction conditions to avoid the acetylene polyinsertion and/or other side reactions from the organonickel intermediates. In this context, the beneficial role of acetate ion on the outcome of the reaction is rationalized. This process leading to the formation of bicycloadducts with the concomitant formation of up to six C-C bonds, with high regio- and stereoselectivity, can be useful in the synthesis of natural products as exemplified by the easy preparation of [5-5-5] tricyclic compound 14 from a 1:1 cis and trans isomeric mixture of 6-acetoxy-3-bromocyclooctene (11). A plausible general reaction mechanism is proposed that is consistent with all the products obtained.
