Conformation of azole compounds

Application of Molecular Orbital Calculations To Estimate the Active Conformation of Azole Compounds... 

Molecular orbital calculations were introduced to estimate the active conformations of azole compounds at an enzyme active site. The computed data were discussed referring to the spectroscopic information and utilized for the steric fit evaluation. 

A group of Italian workers from Modena, led by Professor Taddei, has reviewed published work on the conformations of acyl groups in heterocyclic compounds, including both C-acyl and N-acyl derivatives. The first recent review of the basicity and acidity of azoles, covering both gas-phase and solution measurements, is presented by a group of Spanish workers (Catalan et al.). H. Weber has summarized the considerable recent progress in oxidative transformations of heteroaromatic iminium salts. 

Acidity of azoles, basicity and, 41, 187 Acridines, heterocycle-fused, 70, 89 Acyl groups in heterocyclic compounds, conformations of, 41, 75 Acyclonucleosides, xeco-nucleosides, 67, 391 eco-nucleosides, 68, 1 tri-, tetra-, and penta-seco-nucleosides,... 

Acidity of azoles, basicity and, 41, 187 Acyl groups in heterocyclic compounds, conformations of, 41, 75 Advances... 

In Table 7 are shown some C-H coupling constants for a variety of substituted 1,2,3-triazoles. Furthermore, NMR spectral data of M-acetyl-azoles (39) and -benzazoles (40) have been compared with data for the corresponding iV-methyl compounds in order to obtain information about the conformation of the acetyl compounds (78JCS(P2)99). These results are given in Table 8. 

To estimate the conformations of (I) and (II) at the enzyme active site of fungi or plants, IR and H-NMR spectra of the azole compounds in solutions were measured. From the results of mode of action and binding assay, (I) and (II) are considered to locate in the close proximity to the prosthetic porphyrin group of cytochrome P-450 enzymes. The polarity of macromolecules close to the porphyrin moiety of apohemog1obin has been determined by fluorescence study to be similar to that of n-octanol (1 0)> In our study, carbon tetrachloride and deuterioch1 oroform of which polarities were similar to that of n-octanol were used. 

These data might support our results regarding the active conformations of the azole compounds at the enzyme active site(s). 

We estimated the active conformations of two azole compounds following the strategy proposed above and discussed the interaction between the chemicals and the target sites of macromolecules at the molecular level. The followings are proposed in our study. 

Based on these results, the proposed mode of action of uniconazole (ES pure) is illustrated as an example in Figure 11. Although each of the methods used in this study is already known, the combined application of these methods enables to reduce the number of conceivable active conformations and hence the steric fit evaluation can be performed with high accuracy. The remaining problem is how the azole compounds interact with the non-active sites of enzymes. This is surely related to the difference of biological activity between the optical isomers. 

Heterocycles with endo- and exo Si-Si multiple bonds 04YGK94. Hydrazide-based hypercoordinate silicon compounds (Si-helates) 04MI4. Organometallic complexes of silicon analogs of azoles 03AHC(85)1. Relationship between photophysical properties and conformation of cyclic oligosi-lanes with two or more silicon atoms 02YGK762. 

Some triazepinones in which one of the nitrogen atoms belongs to a fused azole moiety have been reported. For instance, compound 63 was prepared (74JHC751) and its X-ray structure determined (75CSC317). Similarly, and NMR spectra and X-ray structural determination of 64 revealed that this compound exists as a 3//-tautomer with the 1,2,4-triazepine ring in a distorted boat conformation (88T7185). 

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