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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.

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

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a) TFA, dichloroethane, microwave irradiation (MWI): 120 °C, 140 s (10 a–d: 77 %, 86 %, 77 and 68 %, respectively); b) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH (11 a–d: 66, 58, 53 and 66 %, respectively).
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sch1: a) TFA, dichloroethane, microwave irradiation (MWI): 120 °C, 140 s (10 a–d: 77 %, 86 %, 77 and 68 %, respectively); b) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH (11 a–d: 66, 58, 53 and 66 %, respectively).

Mentions: Coumarins substituted with electron-donating groups in position 7 such as 7-methoxy and 7-diethylamino coumarins are frequently used fluorophores (Figure 1). The linker to the pilicide/curlicide central fragment was preferred through the 4 position on the coumarins to resemble the geometry of the C7 naphthyl substituent in 2 and 3. Consequently, the 7-methoxy coumarin-4-yl acetic acid was first coupled to its corresponding acyl Meldrum’s acid derivative 8 using standard conditions.10 On the basis of previous structure–activity relationships of the pilicide/curlicide central fragment, a phenyl,9, 15 a 3-trifluoromethylphenyl,10, 22 a 2-thiophenyl,17 and a cyclopropyl9, 15 were selected as substituents on the Δ2-thiazolines (9 a–d). Reacting 8 with the 9 a–d in the acyl ketene imine cyclocondensation gave coumarin-substituted thiazolo ring-fused 2-pyridones 10 a–d in 68–86 % yield (Scheme 1). Compounds 10 a–d were next subjected to hydrolysis to give the corresponding carboxylic acids 11 a–d in 53–66 % yield.


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) TFA, dichloroethane, microwave irradiation (MWI): 120 °C, 140 s (10 a–d: 77 %, 86 %, 77 and 68 %, respectively); b) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH (11 a–d: 66, 58, 53 and 66 %, respectively).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch1: a) TFA, dichloroethane, microwave irradiation (MWI): 120 °C, 140 s (10 a–d: 77 %, 86 %, 77 and 68 %, respectively); b) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH (11 a–d: 66, 58, 53 and 66 %, respectively).
Mentions: Coumarins substituted with electron-donating groups in position 7 such as 7-methoxy and 7-diethylamino coumarins are frequently used fluorophores (Figure 1). The linker to the pilicide/curlicide central fragment was preferred through the 4 position on the coumarins to resemble the geometry of the C7 naphthyl substituent in 2 and 3. Consequently, the 7-methoxy coumarin-4-yl acetic acid was first coupled to its corresponding acyl Meldrum’s acid derivative 8 using standard conditions.10 On the basis of previous structure–activity relationships of the pilicide/curlicide central fragment, a phenyl,9, 15 a 3-trifluoromethylphenyl,10, 22 a 2-thiophenyl,17 and a cyclopropyl9, 15 were selected as substituents on the Δ2-thiazolines (9 a–d). Reacting 8 with the 9 a–d in the acyl ketene imine cyclocondensation gave coumarin-substituted thiazolo ring-fused 2-pyridones 10 a–d in 68–86 % yield (Scheme 1). Compounds 10 a–d were next subjected to hydrolysis to give the corresponding carboxylic acids 11 a–d in 53–66 % yield.

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