439592-20-8

Upstream product

• 610-14-0 2-nitrobenzyl chloride 
• 504-02-9 1,3-cylohexanedione 
• 115128-99-9 3-methyoxy-2-(2-nitrobenzoyl)-2-cyclohexen-1-one 
• 157034-90-7 3-chloro-2-(2-nitrobenzoyl)-1,3-cyclohexadien-1-ol 

Downstream Products

• 115128-99-9 3-methyoxy-2-(2-nitrobenzoyl)-2-cyclohexen-1-one 
• 157034-90-7 3-chloro-2-(2-nitrobenzoyl)-1,3-cyclohexadien-1-ol 

Relevant academic research and scientific papers

1H NMR, 13C NMR, and computational DFT studies of the structure of 2-acylcyclohexane-1,3-diones and their alkali metal salts in solution

1H and 13C NMR spectra of 2-acyl-substituted cyclohexane-1,3-diones (acyl = formyl, 1; 2-nitrobenzoyl, 2; 2-nitro-4-trifluoromethylbenzoyl, 3) and lithium sodium and potassium salts of 1 have been measured. The compound 3, known as NTBC, is a life-saving medicine applied in tyrosinemia type I. The optimum molecular structures of the investigated objects in solutions have been found using the DFT method with B3LYP functional and 6-31G** and/or 6-311G(2d,p) basis set. The theoretical values of the NMR parameters of the investigated compounds have been calculated using GIAO DFT B3LYP/6-311G(2d,p) method. The theoretical data obtained for compounds 1-3 have been exploited to interpret their experimental NMR spectra in terms of the equilibrium between different tautomers. It has been found that for these triketones an endo-tautomer prevails. The differences in NMR spectra of the salts of 1 can be rationalized taking into account the size of the cation and the degree of salt dissociation. It seems that in DMSO solution the lithium salt exists mainly as an ion pair stabilized by the chelation of a lithium cation with two oxygen atoms. The activation free energy the of formyl group rotation for this salt has been estimated to be 51.5 kJ/mol. The obtained results suggest that in all the investigated objects, including the free enolate ions, all atoms directly bonded to the carbonyl carbons lie near the same plane. Some observations concerning the chemical shift changes could indicate strong solvation of the anion of 1 by water molecules. Implications of the results obtained in this work for the inhibition mechanism of (4-hydroxyphenyl) pyruvate dioxygenase by NTBC are commented upon.

Isomerization of enol esters derived from 2-acyl-1,3-cyclohexanediones: Mechanism and driving force

A series of 2-acyl-1,3-cyclohexanediones were prepared and isomerization mechanisms of the corresponding enol esters were investigated. The driving force for this migration is likely that the intrinsic electrostatic repulsion between the 2-acyl oxygen atom and the two 1,3-diketone oxygens caused deformation of enol esters from planarity and resulted in their high susceptibility to enolization and subsequent isomerization.

Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors

A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1 -9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations between the results of enzyme inhibition, ferric chloride tests, and the conformational analysis suggested that the tight binding between triketonetype inhibitors and 4-HPPD is likely due to chelation of the enzyme-bound ferric iron with the enol tautomer of 1,3-diketone moiety of the triketones. The presence of a 2-carbonyl group in the triketone is an essential structural feature for potent 4-HPPD inhibition. Modification of the 3-carbonyl group of triketone moiety to other functionality will reduce the overall planarity and thus prevent keto-enol tautomerization, resulting in a decrease or lack of inhibition activity.