19909-99-0Relevant 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.
Intramolecular Meta Photocycloaddition of Conformationally Restrained 5-Phenylpent-1-enes. Part I: Bichromophoric Cyclohexane Derivatives
Barentsen, Helma M.,Talman, Edger G.,Piet, Dennis P.,Cornelisse, Jan
, p. 7469 - 7494 (2007/10/02)
The cis isomers of 1-allyl-2-phenycyclohexane and 1-benzyl-2-vinylcyclohexane yield predominantly 1,3 addition, while the trans isomers show a high selectivity for 2,6 addition, which is explained by steric interactions.Introduction of a third substituent, OH or OCH3, on the alkenyl substituted carbon of the cyclohexane ring gives almost exclusively 1,3 addition.This can mostly be explained in terms of more steric hindrance in the conformations leading to 2,6 addition.From the results described it can be concluded that for 2,6 additon two conformations are available, while the energy difference between the 1,3 conformations is much larger and therefore a completely stereoselective 1,3 addition is found (except for 6).
SYNTHESIS OF CYCLOHEXYLALIPHATIC ACIDS AND THEIR PHARMACOLOGICAL PROPERTIES
Kuchar, Miroslav,Brunova, Bohumila,Grimova, Jaroslava,Vanecek, Stanislav,Holubek, Jiri
, p. 2896 - 2908 (2007/10/02)
A series of substituted cyclohexylacetic acids I has been obtained by hydrogenation of the unsaturated analogues II and III.Esters of these analogues were prepared by the Horner-Wittig reaction of the corresponding cyclohexanones IV and/or 2-cyclohexenones V with triethyl phosphonoacetate.These esters were obtained in two isomeric forms (Z and E), differing in the double bond in the exo-position.The derivatives with a substituent in the 2-position exhibited a partial shift of the double bond to the cyclohexane ring; this shift was especially marked in the 2-phenyl derivative.With the acids I-III, activation of fibrinolysis was assessed by the hanging clot method; the anti-inflammatory effect was assessed by inhibition of two experimental model inflammations.The regression equation relating fibrinolytic capacity to lipophilicity was a quadratic one, the logarithm of optimum lipophilicity being log Popt = 5.55.A qualitative assessment of the anti-inflammatory effect in relation to lipophilicity suggests that log Popt is probably higher than with arylaliphatic acids.These acids seem to have an active site different from that of the acids I-III.
