Design, Synthesis, and Analysis of the Quantitative Structure–Activity Relationships of 4-Phenyl-acyl-substituted 3-(2,5-Dimethylphenyl)-4-hydroxy-1-azaspiro[4.5]dec-3-ene-2,8-dione Derivatives

Abstract

A series of 4-phenyl-acyl-substituted 3-(2,5-dimethylphenyl)-4-hydroxy-1-azaspiro[4.5]dec-3-ene-2,8-dione derivatives were designed and synthesized, and their structures were characterized using (1)H NMR (or (13)C NMR), mass spectrometry, and elemental analysis. The bioactivities of the new compounds were evaluated. These compounds exhibited good inhibition activities against bean aphids (Aphis fabae) and carmine spider mite (Tetranychus cinnabarinus), and 4-phenyl acyl esters showed stronger bioactivity than 4-arylesterases and alkyl esters. The results showed that compound 8-I-e, which contains a para-methoxy group on the phenyl acyl, and compound 8-I-m, which contains a para-trifluoromethyl group on the phenyl acyl, displayed potent insecticidal activity against A. fabae and T. cinnabarinus respectively. The insecticidal activity showed a clear structure-activity relationship, confirming the importance of the flexible bridge. The DFT/B3LYP/6-31(d) level method was used to calculate molecular geometries and electronic descriptors. These factors included total energy, charge distribution, and the linear orbital level of the title compounds. Quantitative structure-activity relationship studies were performed on these compounds using quantum-chemical and physicochemical parameters as independent variables and insecticidal activity as a dependent variable. Insecticidal activity was most closely correlated (r > 0.8) with quantum chemical and physicochemical parameters.

Synthesis, antifungal activity, and QSAR study of novel trichodermin derivatives

“…That is, a lower log P value will result in higher inhibitory activity, and high lipophilicity may be beneficial for derivatives to penetrate into the body of fungus. It is worth noting that HOMO and LUMO are two most important factors which represent the ability to donate and accept electron, respectively [15]. Hardness is defined as the energy difference between HOMO and LUMO, which is widely used as a measure of chemical reactivity with bigger gaps implying larger excitation energies and higher stability [24].…”

Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors

“…This result indicated that the introduction of phenylacetyl moiety gave higher bioactivities than that of the benzoyl group at position C‐4. This may be because there was a flexible methylene bridge in the phenylacetyl group . Furthermore, among compounds 5e to 5o , which had phenylacetyl groups at position C‐4, only compound 5e displayed very low efficacy because the bridge had great steric hindrance via the introduction of the isopropyl group.…”

“…Column chromatographic purification was carried out using silica gel. The CLOGP values were calculated using ChemBio3D Ultra 12.0 software . The reagents were all analytically or chemically pure.…”

“…The CLOGP values were calculated using ChemBio3D Ultra 12.0 software. 22,23 The reagents were all analytically or chemically pure. All anhydrous solvents were dried and purified by standard techniques prior to use.…”

“…This may be because there was a flexible methylene bridge in the phenylacetyl group. 23 Furthermore, among compounds 5e to 5o, which had phenylacetyl groups at position C-4, only compound 5e displayed very low efficacy because the bridge had great steric hindrance via the introduction of the isopropyl group. Additionally, it is worth noting that compound 5k (LC 50 = 58.50 mg L −1 ) clearly exhibited lower inhibitory potency against bean aphids by comparison with compounds 5f and 5h (LC 50 = 0.42 and 0.28 mg L −1 ).…”