Stereoselective Synthesis and in Vitro Antifungal Evaluation of (E)- and (Z)-Imidazolylchromanone Oxime Ethers

Imidazolylchromanones containing alkyl side chain as lanosterol 14α-demethylase inhibitors: synthesis, antifungal activity and docking study

“…Previously, Ji et al designed 2-alkylchromanone and their oximes ( Figure 1, structure B) as non-azole inhibitors of 14a-demethylase 9 . Moreover, we have reported 3-imidazolyl chromanone oxime ethers as antifungal agents 10 . In this study, we incorporated imidazole ring on the 3-position of 2-alkylchromanones to design new inhibitors of 14a-demethylase and potential antifungal agents ( Figure 1, structure C).…”

“…The (E)-or (Z)-geometry was readily identified by 1 H NMR, based on the deshielding effect of the oxime oxygen. According to the previous studies, when the (E)-isomer is produced in the oximation reaction, the H-5 proton of chroman ring is significantly deshielded (48.5 ppm) with respect to the parent ketone (58 ppm) 10,16 . As seen in Table 1, the chemical shifts of oxime derivatives (5) are virtually the same as those of ketones (4) and no signal was detected around 8.5 ppm.…”

Azolylchromans as a novel scaffold for anticonvulsant activity

“…[13][14][15][16] In addition, certain azolylchromanone derivatives were synthesized in our laboratory, as intermediates for achieving some antifungal agents. [17][18][19] These compounds can be considered as conformationally constrained analogs of (arylalkyl)azoles (loreclezole 1, nafimidone 2, and denzimole 3) (Fig. 1) and consist of a chroman ring that, in itself, shows some anticonvulsant activity.…”

“…[17][18][19] Thus, ring closure of compound 7 by paraformaldehyde or acetaldehyde in acetic acid at 90-100°C gave the corresponding 3-azolylchroman-4-one derivatives 4. In the case of 2-methylchromanone derivatives 4c, 4d, 4i, and 4j, the configuration of methyl group respect to azole ring was assigned as trans-configuration, according to the large 1 7 by refluxing with triethyl orthoformate or triethyl orthoacetate afforded 3-(1,2,4-triazol-4-yl)chromen-4-ones 6.…”

“…Ketones 4 were converted to the pure (Z)-oxime derivatives (Z)-5 by stirring with 3 equiv of HON-H 2 AEHCl in methanol at room temperature. [17][18][19] Another stereoselective synthetic pathway was used to obtain the (E)-stereoisomers of oximes 5. Thus, reaction of 3-bromo-4-chromanone oxime 8 with imidazole or 1,2,4-triazole afforded (E)-oximes (E)-5.…”