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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) TFA, dichloroethane, MWI: 120 °C, 140 s (13 a,b: 92 and 87 %, respectively); b) 14 a or 14 b, LiHMDS, THF, −35 °C, 1 h (15 a–d: 74, 82, 83 and 75 %, respectively); c) For 16 a,c: 0.1 M aq LiOH, THF/MeOH (4:1) 1.5 h; ii) AcOH (16 a,c: 86 and 82 %, respectively), For 16 b,d: i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH (16 b,d: 91 and 81 %, respectively).
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sch2: a) TFA, dichloroethane, MWI: 120 °C, 140 s (13 a,b: 92 and 87 %, respectively); b) 14 a or 14 b, LiHMDS, THF, −35 °C, 1 h (15 a–d: 74, 82, 83 and 75 %, respectively); c) For 16 a,c: 0.1 M aq LiOH, THF/MeOH (4:1) 1.5 h; ii) AcOH (16 a,c: 86 and 82 %, respectively), For 16 b,d: i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH (16 b,d: 91 and 81 %, respectively).

Mentions: The photophysical evaluation of 11 a–d showed relatively low quantum yields of fluorescence (ΦF, Table 1). The C8 phenyl-substituted 11 a displayed highest quantum yield (ΦF=5 %), followed by the C8 3-trifluomethylphenyl-substituted 11 b (ΦF=1 %), the C8 2-thiophenyl-substituted 11 c (ΦF=0.7 %), and finally the C8 cyclopropyl-substituted 11 d (ΦF=0.4 %). These results may be due to a quenching effect of the fluorophore by the neighboring dihydrothiazolo ring-fused 2-pyridone pilicide/curlicide central fragment. In an attempt to circumvent this, the linker between the fluorophore and the 2-pyridone central fragment was increased by a one carbon extension. This was realized by using deprotonated 4-methyl coumarins as nucleophiles on bromomethyl-substituted 2-pyridone central fragments. By using this strategy the introduction of both a 7-methoxy-substituted coumarin and a 7-diethylamine-substituted coumarin could be accomplished (Scheme 2). The intermediate bromomethyl-substituted 2-pyridone central fragments (13 a and 13 b) were synthesized following a previously published procedure.23 Addition of lithiated coumarins (14 a and 14 b) to 13 a and 13 b generated the one carbon extended coumarin-substituted ring-fused 2-pyridones 15 a–d in 74–83 % yield. Subsequent hydrolysis rendered 16 a–d in high yields (81–91 %; Scheme 2).


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, MWI: 120 °C, 140 s (13 a,b: 92 and 87 %, respectively); b) 14 a or 14 b, LiHMDS, THF, −35 °C, 1 h (15 a–d: 74, 82, 83 and 75 %, respectively); c) For 16 a,c: 0.1 M aq LiOH, THF/MeOH (4:1) 1.5 h; ii) AcOH (16 a,c: 86 and 82 %, respectively), For 16 b,d: i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH (16 b,d: 91 and 81 %, respectively).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch2: a) TFA, dichloroethane, MWI: 120 °C, 140 s (13 a,b: 92 and 87 %, respectively); b) 14 a or 14 b, LiHMDS, THF, −35 °C, 1 h (15 a–d: 74, 82, 83 and 75 %, respectively); c) For 16 a,c: 0.1 M aq LiOH, THF/MeOH (4:1) 1.5 h; ii) AcOH (16 a,c: 86 and 82 %, respectively), For 16 b,d: i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH (16 b,d: 91 and 81 %, respectively).
Mentions: The photophysical evaluation of 11 a–d showed relatively low quantum yields of fluorescence (ΦF, Table 1). The C8 phenyl-substituted 11 a displayed highest quantum yield (ΦF=5 %), followed by the C8 3-trifluomethylphenyl-substituted 11 b (ΦF=1 %), the C8 2-thiophenyl-substituted 11 c (ΦF=0.7 %), and finally the C8 cyclopropyl-substituted 11 d (ΦF=0.4 %). These results may be due to a quenching effect of the fluorophore by the neighboring dihydrothiazolo ring-fused 2-pyridone pilicide/curlicide central fragment. In an attempt to circumvent this, the linker between the fluorophore and the 2-pyridone central fragment was increased by a one carbon extension. This was realized by using deprotonated 4-methyl coumarins as nucleophiles on bromomethyl-substituted 2-pyridone central fragments. By using this strategy the introduction of both a 7-methoxy-substituted coumarin and a 7-diethylamine-substituted coumarin could be accomplished (Scheme 2). The intermediate bromomethyl-substituted 2-pyridone central fragments (13 a and 13 b) were synthesized following a previously published procedure.23 Addition of lithiated coumarins (14 a and 14 b) to 13 a and 13 b generated the one carbon extended coumarin-substituted ring-fused 2-pyridones 15 a–d in 74–83 % yield. Subsequent hydrolysis rendered 16 a–d in high yields (81–91 %; Scheme 2).

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