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Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

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ABSTRACT

This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyranosides with an elongated hydrophobic hydrocarbon chain. The new N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides and their O-acetyl derivatives were analyzed via 1H and 13C NMR spectroscopy. The mutagenic activity of the newly synthesized QAS was investigated using two different techniques: The Vibrio harveyi luminescence assay and the Ames test. The obtained results support previous findings contesting QAS safety and indicate that QAS, specifically pyridinium derivatives, might be mutagenic.

No MeSH data available.


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Reagents and conditions; I: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 3 h, rt, ([32] compound 2 36% yield); II: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 72 h (compound 2 17% yield + compound 3 24% yield), rt; III: 0.82 M MeONa/MeOH, rt, 24 h; IV: N(CH3)3/EtOH, 70 °C, 5 h (4a, 6a), 18 h (5a, 7a); V: Py, 70 °C, 24 h (4b, 6b), 36 h (5b, 7b).
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C1: Reagents and conditions; I: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 3 h, rt, ([32] compound 2 36% yield); II: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 72 h (compound 2 17% yield + compound 3 24% yield), rt; III: 0.82 M MeONa/MeOH, rt, 24 h; IV: N(CH3)3/EtOH, 70 °C, 5 h (4a, 6a), 18 h (5a, 7a); V: Py, 70 °C, 24 h (4b, 6b), 36 h (5b, 7b).

Mentions: We synthesized N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium salts to determine the effect of the linker length in QASs on their mutagenic potential (Scheme 1). The main product of the first step of the synthesis was the 1,2-trans-glucoside, i.e., 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside (2) in 36% yield [32]. By using a Lewis acid (BF3·Et2O) as an activator and by extending the reaction time to 72 h, the product with configuration α-D-gluco, i.e., 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-α-D-glucopyranoside (3) in 24% yield and 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside (2) in 17% yield were obtained. 6-Bromohexyl 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside (2) and 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-α-D-glucopyranoside (3) were then reacted with trimethylamine in ethanol and with pyridine to assess the effect of the sugar substituent on the course of quaternization. Compounds 4a, 4b, 6a, 6b were obtained in almost quantitative yields (92–99%). Since de-O-acetylated salts could not be obtained using sodium methanolate in methanol, an alternative route involving the reaction of 6-bromohexyl D-glucopyranoside (2′ [32] or 3′) with tertiary amines (trimethylamine in ethanol and with pyridine) was applied; the yields were of 90–94%. Shifting the pyranose leaving group (halogen) by six carbon atoms from C1 makes it easier to design the QAS. All the newly synthesized N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides were water soluble. The identities of all compounds were confirmed by 1H and 13C NMR.


Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates
Reagents and conditions; I: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 3 h, rt, ([32] compound 2 36% yield); II: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 72 h (compound 2 17% yield + compound 3 24% yield), rt; III: 0.82 M MeONa/MeOH, rt, 24 h; IV: N(CH3)3/EtOH, 70 °C, 5 h (4a, 6a), 18 h (5a, 7a); V: Py, 70 °C, 24 h (4b, 6b), 36 h (5b, 7b).
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C1: Reagents and conditions; I: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 3 h, rt, ([32] compound 2 36% yield); II: HO(CH2)6Br, BF3·Et2O/CH2Cl2, 1 h 0 °C → 72 h (compound 2 17% yield + compound 3 24% yield), rt; III: 0.82 M MeONa/MeOH, rt, 24 h; IV: N(CH3)3/EtOH, 70 °C, 5 h (4a, 6a), 18 h (5a, 7a); V: Py, 70 °C, 24 h (4b, 6b), 36 h (5b, 7b).
Mentions: We synthesized N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium salts to determine the effect of the linker length in QASs on their mutagenic potential (Scheme 1). The main product of the first step of the synthesis was the 1,2-trans-glucoside, i.e., 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside (2) in 36% yield [32]. By using a Lewis acid (BF3·Et2O) as an activator and by extending the reaction time to 72 h, the product with configuration α-D-gluco, i.e., 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-α-D-glucopyranoside (3) in 24% yield and 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside (2) in 17% yield were obtained. 6-Bromohexyl 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside (2) and 6-bromohexyl 2',3',4',6'-tetra-O-acetyl-α-D-glucopyranoside (3) were then reacted with trimethylamine in ethanol and with pyridine to assess the effect of the sugar substituent on the course of quaternization. Compounds 4a, 4b, 6a, 6b were obtained in almost quantitative yields (92–99%). Since de-O-acetylated salts could not be obtained using sodium methanolate in methanol, an alternative route involving the reaction of 6-bromohexyl D-glucopyranoside (2′ [32] or 3′) with tertiary amines (trimethylamine in ethanol and with pyridine) was applied; the yields were of 90–94%. Shifting the pyranose leaving group (halogen) by six carbon atoms from C1 makes it easier to design the QAS. All the newly synthesized N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides were water soluble. The identities of all compounds were confirmed by 1H and 13C NMR.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyranosides with an elongated hydrophobic hydrocarbon chain. The new N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides and their O-acetyl derivatives were analyzed via 1H and 13C NMR spectroscopy. The mutagenic activity of the newly synthesized QAS was investigated using two different techniques: The Vibrio harveyi luminescence assay and the Ames test. The obtained results support previous findings contesting QAS safety and indicate that QAS, specifically pyridinium derivatives, might be mutagenic.

No MeSH data available.


Related in: MedlinePlus