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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) DCC, Meldrum’s acid, DMAP, CH2Cl2, 0 °C RT, 8 h, 82 %; b) 9 a, TFA, dichloroethane, MWI: 120 °C, 140 s, 85 %; c) i) 35, (NH4)2MoO4, toluene, reflux soxhlet (3 MS), 6 h; ii) 32, TFA, toluene, reflux soxhlet (3 MS), 2 h, 73 %; d) starting from 34, mCPBA, CH2Cl2, RT, 15 min, 80 %; e) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH, 88 %; f) i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH, 88 %.
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sch6: a) DCC, Meldrum’s acid, DMAP, CH2Cl2, 0 °C RT, 8 h, 82 %; b) 9 a, TFA, dichloroethane, MWI: 120 °C, 140 s, 85 %; c) i) 35, (NH4)2MoO4, toluene, reflux soxhlet (3 MS), 6 h; ii) 32, TFA, toluene, reflux soxhlet (3 MS), 2 h, 73 %; d) starting from 34, mCPBA, CH2Cl2, RT, 15 min, 80 %; e) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH, 88 %; f) i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH, 88 %.

Mentions: With these two C8 BODIPY-substituted compounds (28 and 31) in hand, introduction of BODIPY in position C7 on the central fragment was next investigated. Coupling the BODIPY carboxylic acid 24 with Meldrum’s acid using standard coupling conditions and a simple MeOH trituration as purification gave the BODIPY-substituted acyl Meldrum’s acid derivative 32 in 82 % yield (Scheme 6). From this versatile intermediate the following acylketene imine cyclocondensation to the C7 BODIPY substituted pilicide/curlicide central fragment 33 was performed in 88 % yield. Sequential hydrolysis gave the corresponding carboxylic acid 34 (Scheme 6). The photophysical properties of 34 suggest, in analogy with the coumarins, that the BODIPY fluorophore also seems to be partially quenched in this position (ΦF=11 %, 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) DCC, Meldrum’s acid, DMAP, CH2Cl2, 0 °C RT, 8 h, 82 %; b) 9 a, TFA, dichloroethane, MWI: 120 °C, 140 s, 85 %; c) i) 35, (NH4)2MoO4, toluene, reflux soxhlet (3 MS), 6 h; ii) 32, TFA, toluene, reflux soxhlet (3 MS), 2 h, 73 %; d) starting from 34, mCPBA, CH2Cl2, RT, 15 min, 80 %; e) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH, 88 %; f) i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH, 88 %.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch6: a) DCC, Meldrum’s acid, DMAP, CH2Cl2, 0 °C RT, 8 h, 82 %; b) 9 a, TFA, dichloroethane, MWI: 120 °C, 140 s, 85 %; c) i) 35, (NH4)2MoO4, toluene, reflux soxhlet (3 MS), 6 h; ii) 32, TFA, toluene, reflux soxhlet (3 MS), 2 h, 73 %; d) starting from 34, mCPBA, CH2Cl2, RT, 15 min, 80 %; e) i) 0.1 M aq LiOH, THF/MeOH (4:1); ii) AcOH, 88 %; f) i) LiBr, TEA, MeCN (+2 v/v % H2O), RT, 3 h; ii) AcOH, 88 %.
Mentions: With these two C8 BODIPY-substituted compounds (28 and 31) in hand, introduction of BODIPY in position C7 on the central fragment was next investigated. Coupling the BODIPY carboxylic acid 24 with Meldrum’s acid using standard coupling conditions and a simple MeOH trituration as purification gave the BODIPY-substituted acyl Meldrum’s acid derivative 32 in 82 % yield (Scheme 6). From this versatile intermediate the following acylketene imine cyclocondensation to the C7 BODIPY substituted pilicide/curlicide central fragment 33 was performed in 88 % yield. Sequential hydrolysis gave the corresponding carboxylic acid 34 (Scheme 6). The photophysical properties of 34 suggest, in analogy with the coumarins, that the BODIPY fluorophore also seems to be partially quenched in this position (ΦF=11 %, 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