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Design and synthesis of fluorescent pilicides and curlicides: bioactive tools to study bacterial virulence mechanisms.

Chorell E, Pinkner JS, Bengtsson C, Edvinsson S, Cusumano CK, Rosenbaum E, Johansson LB, Hultgren SJ, Almqvist F - Chemistry (2012)

Bottom Line: To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized.This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores.We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Umeå University, 90187 Umeå, Sweden.

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a) i) (COCl)2, DMF, CH2Cl2, RT, 1 h; ii) TEA, BF3⋅OEt2, 2,4-dimethylpyrrole, dichloroethane, MWI: 140 °C, 50 min, 15 %; b) 0.1 M aqueous LiOH, THF, RT, 1 h; ii) H+, 84 %.
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sch5: a) i) (COCl)2, DMF, CH2Cl2, RT, 1 h; ii) TEA, BF3⋅OEt2, 2,4-dimethylpyrrole, dichloroethane, MWI: 140 °C, 50 min, 15 %; b) 0.1 M aqueous LiOH, THF, RT, 1 h; ii) H+, 84 %.

Mentions: The photophysical evaluation of 28 gave a quantum yield of 10 %, which is surprisingly low for a BODIPY-substituted compound (Table 1). We hypothesized that photo-quenching was a possible reason for this and thus the use of an aryl linker between the fluorophore and the central fragment could circumvent the problem. This would not only increase the distance between the fluorophore and the pilicide/curlicide central fragment but it would also restrict the rotation of the 1,3,5,7-tetramethyl-substituted BODIPY, which is known to generate higher quantum yields.20 Exchange of the methylene linker for a phenyl results in the need for a revised synthetic approach. A recent publication shows that it is possible to introduce a benzoic acid in the C8 position of the pilicide/curlicide central fragment by Suzuki–Miyaura couplings.27 From this benzoic acid derivative, the transformation into the desired C8 BODIPY-substituted central fragment seemed feasible. Consequently, 2-pyridone 29 was treated with oxalyl chloride followed by reaction with 2,4-dimethylpyrrole in the presence of BF3⋅OEt2 and triethylamine to give the desired C8 BODIPY-substituted central fragment 30 in 15 % yield. Subsequent hydrolysis was straightforward for this BODIPY derivative, giving the corresponding carboxylic acid 31 in 84 % yield (Scheme 5). As hypothesized, introduction of the phenyl spacer in the C8 position increased the quantum yield of 31 to a satisfactory 67 % (Table 1).


Design and synthesis of fluorescent pilicides and curlicides: bioactive tools to study bacterial virulence mechanisms.

Chorell E, Pinkner JS, Bengtsson C, Edvinsson S, Cusumano CK, Rosenbaum E, Johansson LB, Hultgren SJ, Almqvist F - Chemistry (2012)

a) i) (COCl)2, DMF, CH2Cl2, RT, 1 h; ii) TEA, BF3⋅OEt2, 2,4-dimethylpyrrole, dichloroethane, MWI: 140 °C, 50 min, 15 %; b) 0.1 M aqueous LiOH, THF, RT, 1 h; ii) H+, 84 %.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569613&req=5

sch5: a) i) (COCl)2, DMF, CH2Cl2, RT, 1 h; ii) TEA, BF3⋅OEt2, 2,4-dimethylpyrrole, dichloroethane, MWI: 140 °C, 50 min, 15 %; b) 0.1 M aqueous LiOH, THF, RT, 1 h; ii) H+, 84 %.
Mentions: The photophysical evaluation of 28 gave a quantum yield of 10 %, which is surprisingly low for a BODIPY-substituted compound (Table 1). We hypothesized that photo-quenching was a possible reason for this and thus the use of an aryl linker between the fluorophore and the central fragment could circumvent the problem. This would not only increase the distance between the fluorophore and the pilicide/curlicide central fragment but it would also restrict the rotation of the 1,3,5,7-tetramethyl-substituted BODIPY, which is known to generate higher quantum yields.20 Exchange of the methylene linker for a phenyl results in the need for a revised synthetic approach. A recent publication shows that it is possible to introduce a benzoic acid in the C8 position of the pilicide/curlicide central fragment by Suzuki–Miyaura couplings.27 From this benzoic acid derivative, the transformation into the desired C8 BODIPY-substituted central fragment seemed feasible. Consequently, 2-pyridone 29 was treated with oxalyl chloride followed by reaction with 2,4-dimethylpyrrole in the presence of BF3⋅OEt2 and triethylamine to give the desired C8 BODIPY-substituted central fragment 30 in 15 % yield. Subsequent hydrolysis was straightforward for this BODIPY derivative, giving the corresponding carboxylic acid 31 in 84 % yield (Scheme 5). As hypothesized, introduction of the phenyl spacer in the C8 position increased the quantum yield of 31 to a satisfactory 67 % (Table 1).

Bottom Line: To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized.This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores.We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Umeå University, 90187 Umeå, Sweden.

Show MeSH
Related in: MedlinePlus