Synthesis and antibacterial activities of acylide derivatives bearing an aryl-tetrazolyl chain

Figures & data

Figure 1 Synthesis of N2-substituted 5-aryl-tetrazolyl alkylamines.

Notes: Reagents and condition: (a) NaN₃, NH₄CI, DMF, 130°C and (b) i) I₂, aq NH₃, rt; ii) NaN₃, ZnBr; reflux; (c) N-(3-bromopropyl)phthalimide, N-(4-bromobutyl) phthalimide or N-(5-bromopentyl)phthalimide, KCO₃, DMF, 80°C: (d) NH₂NH₂ · HO, EtOH/CH₃CN, reflux.
Abbreviations: Ar, aromatic nucleus; DMF, N, N-dimethyl formamide; aq, aqueous; rt, room temperature; EtOH, ethanol.

Figure 2 Synthesis of N1-submitted and N2-submitted 5-aryl-tetrazolyl alkylamines.

Notes: Reagents and condition: (c) N-(3-bromopropyl)phthalimide, N-(4-bromobutyl)phthalimide or N-(5-bromopentyl)phthalimide, K₂CO₃, DMF, 80°C; (d) NH₂NH₂ · H₂O, EtOH/CH₃CN, reflux.
Abbreviations: DMF, N, N-dimethyl formamide; EtOH, ethanol.

Figure 3 Synthesis of a set of acylide derivatives for compounds 10a–10g.

Notes: Reagents and conditions: (a) Ethylene carbonate, TEA, reflux; (b) HCI, EtOH, H₂O; (c) Ac₂O,TEA, CH₂Cl₂; (d) PivCl, DMAP, CH₂Cl₂, −15°C to rt; (e) CDI, DMAP, CH₂Cl₂, rt; (f) RNH₂, CH₃CN/H₂O, 55°C; (g) CH₃OH, reflux.
Abbreviations: TEA, triethylamine; PivCl, pivaloyl chloride; EtOH, ethanol; CDI, carbonyl diimidazole; DMAP, 4-Dimethylaminopyridine; Ac, acetoxy; rt, room temperature.

Figure 4 Structure synthesized acylides.

Note: *Connection position of R group to the parent compound.
Abbreviations: R, substituted group; Me, methyl.

Table 1 The antibacterial activities of novel acylides in vitro

Compound	Minimum inhibitory concentration, μg/mL
	Staphylococcus aureus		Staphylococcus epidermidis	Pseudomonas aeruginosa		Escherichia coli
	ATCC 25923	ATCC 6538	ATCC 12228	ATCC 1317	ATCC 9027	ATCC 8739	ATCC 25922
ERY	0.5	0.5	0.5	>128	128	32	8
CLA	0.25	0.5	0.25	128	64	16	4
10a	0.25	1	0.125	32	64	16	16
10b	0.25	0.25	0.25	128	32	32	64
10c	1	0.5	0.25	128	128	64	64
10d	0.5	1	0.5	>128	128	64	64
10e	0.125	0.25	0.125	16	8	8	2
10f	0.125	0.125	<0.0625	64	64	16	4
10g	0.125	0.063	<0.0625	64	32	32	16
10h	0.125	0.25	0.125	128	64	32	16
10i	0.25	0.5	0.125	128	64	64	32
10j	0.25	0.5	0.125	64	128	64	64
10k	0.5	0.5	0.25	128	64	64	64
10l	0.5	0.25	0.5	128	128	128	64
10m	0.125	0.5	0.5	128	64	64	64
10n	0.125	0.5	0.5	64	32	16	16
10o	<0.0625	0.125	0.25	16	16	8	4
10p	0.125	0.125	0.25	64	32	32	32
10q	0.25	0.25	0.25	128	128	128	64

Abbreviations: ATCC, American Type Culture Collection; ERY, erythromycin; CLA, clarithromycin.