Synthesis and antifungal activity of novel oxazolidin-2-one-linked 1,2,3-triazole derivatives

Abstract

Novel oxazolidin-2-one-linked 1,2,3-triazole derivatives () were synthesized by straightforward and versatile azide-enolate (3 + 2) cycloaddition. The series of compounds was screened for antifungal activity against four filamentous fungi as well as six yeast species of spp. According to their efficiency and breadth of scope, they can be ordered as > > > , especially in relation to the activity displayed against ATCC-34138, ATCC-28592 and ATCC-8690, compounds, and showed excellent activity against (MIC 0.12, 0.25 and 0.12 μg mL, respectively), better than that of itraconazole (MIC 1 μg ml). The activity of compound (MIC = 2 μg mL) was higher than that observed for the standard antifungal drug (MIC = 8 μg mL) against , while compound displayed an excellent antimycotic activity against (MIC = 2 μg mL 4 μg mL for itraconazole). In addition, we describe herein a novel mild and eco-friendly synthetic protocol for obtaining β-ketosulfones (adducts to afford compounds ) from α-brominated carbonyls in an aqueous nanomicellar medium at room temperature.

Insight into the Antifungals Used to Address Human Infection Due to Trichosporon Spp.: A Scoping Review

“…To improve antifungal activity, studies have used miconazole [ 45 ], 1,4,5-trisubstituted derivatives [ 46 ] and novel oxazolidin-2-one-linked 1,2,3-triazole derivatives [ 47 ]. Against T. cutaneum , the greatest reductions were with the antifungal compound 1-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-5-pentyl-4-(phenylsulfonyl)-1H-1,2,3-triazole (4d) with a MIC of 0.12 μg/ml [ 46 ].…”

The Three-Component Synthesis of 4-Sulfonyl-1,2,3-triazoles via a Sequential Aerobic Copper-Catalyzed Sulfonylation and Dimroth Cyclization

“…4-Sulfonyl-1,2,3-triazole scaffolds possess very promising bioactivities, which include antibacterial [ 1 ] and antifungal agents [ 2 , 3 ], as well as potent antagonists of neutrophil elastase (HLE) [ 4 ] and the human pregnane X receptor (hPXR) [ 5 , 6 , 7 ], as shown in Figure 1 . Additionally, they have found application as (monomeric) anion binders [ 8 ].…”

“…However, several limiting factors remain, such as the necessary multistep synthesis of the alkynyl sulfide [ 14 , 15 , 16 , 17 ] and sulfone starting materials [ 9 , 18 , 19 , 20 ], the use of stoichiometric oxidants for conversion of the thioether into a sulfone, and the high cost of the noble metal catalyst. The most prominent alternative to the AAC synthesis of 4-sulfonyl triazoles is the Dimroth azide–enolate cycloaddition of sulfonyl ketones [ 3 , 21 , 22 , 23 , 24 ]. While previously reported room temperature Dimroth cyclizations furnished 4-sulfonyl triazoles in good to high yields [ 3 , 22 , 23 ], the requirement of prior synthesis and isolation of the sulfonyl ketones reduces their sustainability and attractiveness [ 3 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

“…The most prominent alternative to the AAC synthesis of 4-sulfonyl triazoles is the Dimroth azide–enolate cycloaddition of sulfonyl ketones [ 3 , 21 , 22 , 23 , 24 ]. While previously reported room temperature Dimroth cyclizations furnished 4-sulfonyl triazoles in good to high yields [ 3 , 22 , 23 ], the requirement of prior synthesis and isolation of the sulfonyl ketones reduces their sustainability and attractiveness [ 3 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Additionally, there are two alternative pathways, based on the Wolff triazole synthesis [ 36 , 37 ] and azide–alkene cycloaddition [ 38 , 39 , 40 ] that are both less attractive due to the use of unstable α-diazo-sulfonyl ketones, and the somewhat lower yields or availability of the starting materials.…”

α‐Diazo‐β‐oxosulfones as Partners in the Wolff 1,2,3‐Triazole Synthesis and the Wolff Rearrangement in the Presence of Aromatic Amines

“…Puzzled by the lack of reports in the literature on the involvement of α‐sulfonyl α‐diazocarbonyl compounds 1 (R 1 = SO 2 R) in the Wolff 1,2,3‐triazoles synthesis, we decided to investigate this possibility. Filling this methodology void, we reasoned, would provide a streamlined entry in the 1,5‐disubstituted 4‐sulfonyl 1,2,3‐triazole core which is featured in a range of biologically active compounds such as bromodomain inhibitor 6 , antifungal compound 7 , pregnane X receptor antagonist 8 for attenuation of drug metabolism and anti‐inflammatory GPR43 receptor agonist 9 (Figure ). Notably, such an approach would complement the earlier reported synthesis of similarly substituted 1,2,3‐triazoles by the Dimroth cyclocondensation of β‐keto sulfones with aryl azides …”