A Facile and Efficient Multi‐Gram Synthesis of <i>N</i>‐Protected 5‐(Guanidinocarbonyl)‐1<i>H</i>‐pyrrole‐2‐carboxylic Acids

Schmuck, Carsten; Bickert, Volker; Merschky, Michael; Geiger, Lars; Rupprecht, Daniel; Dudaczek, Jürgen; Wich, Peter; Rehm, Thomas H.; Machon, Uwe

doi:10.1002/ejoc.200700756

Cited by 49 publications

(41 citation statements)

References 25 publications

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“…45,46 All other reagents were purchased from commercial sources and used without further purification. 1 H NMR spectra and 13 C NMR spectra were obtained on a Varian INOVA-400 MHz and Bruker AV-300 MHz Spectrometer, respectively.…”

Section: Methodsmentioning

confidence: 99%

A New Chemosensing Ensemble for Colorimetric Detection of Oxalate in Water

Tang¹,

Liu²

2010

Bulletin of the Korean Chemical Society

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To realize highly selective recognition of oxalate in water, a new chemosensing ensemble that behaves highly selective colorimetric recognition of oxalate in water at pH 7.4 has been developed. The ensemble was constructed by a pyrrole containing mononuclear copper complex and chromeazurol S. The ensemble shows a highly selective recognition of oxalate through an obvious color change from blue to yellow upon the addition of oxalate, whereas, other dicarboxylates such as malonate, succinate, fumarate, maleate, glutarate, adipate, phthalate, isophthalate and terephthalate do not induce any noticeable color changes. The oxalate recognition process is not significantly affected by other coexisting dicarboxylate.

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Section: Methodsmentioning

confidence: 99%

A New Chemosensing Ensemble for Colorimetric Detection of Oxalate in Water

Tang¹,

Liu²

2010

Bulletin of the Korean Chemical Society

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“…[15] Peptide solutions for kinetic measurements were prepared by diluting stock solutions to final concentrations of 2 mm in 50 mm Bis-Tris buffer containing 0.1 % NaN 3 (Bis-Tris = 2-(bis(2-hydroxyethyl)amino)-2-(hydroxymethyl)propane-1,3-diol). The pH value was adjusted by the addition of NaOH.…”

Section: Methodsmentioning

confidence: 99%

“…[14] The peptides were synthesized by solid-phase peptide synthesis as reported previously for HNI, but by attaching the guanidiniocarbonyl pyrrole group to selectively deprotected ornithine residues by using amide-coupling chemistry. [15,16] After deprotection and cleavage from the solid support, the peptides were obtained in 10-20 % yield after reversed-phase HPLC purification and identified by MALDI-TOF MS.…”

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confidence: 99%

Downsizing of Enzymes by Chemical Methods: Arginine Mimics with Low pK_a Values Increase the Rates of Hydrolysis of RNA Model Compounds

Lindgren¹,

Geiger²,

Razkin³

et al. 2009

Angew Chem Int Ed

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“…[21] For the synthesis of the furan building block, the starting compound was the 5-(methoxycarbonyl)furan-2-carboxylic acid [22] (2). By coupling this acid to the mono-Cbz-protected guanidine [21] (3), we obtained the first precursor (5). Subsequent saponification of the methyl ester gave carboxylic acid 7 in excellent yield.…”

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confidence: 99%

Development of Antitrypanosomal and Antiplasmodial Nonpeptidic Cysteine Protease Inhibitors based on N‐Protected‐Guanidino‐Furan and ‐Pyrrole Building Blocks

et al. 2011

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Infectious diseases, such as malaria, leishmaniasis, and African trypanosomiasis (sleeping sickness), are public health problems in more than 90 countries with millions of deaths per year. [1] The drugs mainly used today for chemotherapy, especially against the neglected diseases leishmaniasis and trypanosomiasis, were developed decades ago, lack appropriate efficacy, and give rise to severe side effects. The absence of highly effective vaccines and the inadequate control of insect vectors demand new approaches to drug development. Furthermore, resistance of the pathogens causing malaria (Plasmodium falciparum) and African trypanosomiasis (sleeping sickness caused by Trypanosoma brucei gambiense and T. b. rhodesiense, and nagana in livestock, caused by T. b. brucei) against established drugs has been increasing. Therefore, research to identify new drugs, ideally addressing new targets, is more important than ever. [2] Parasite cysteine proteases of clan CA, family C1 (papain family), [3] are considered to be new promising therapeutic targets. These enzymes, namely falcipains [4] in plasmodia, and rhodesain [5] in T. b. rhodesiense, play important roles in the life cycles of the parasites. Cysteine protease inhibitors have been reported to kill African trypanosomes in vitro and in animal models of the disease, [6] however, it is not yet clear whether rhodesain is the only target of the inhibitors.[7] Proteases of malaria parasites play pivotal roles in the processes of host erythrocyte rupture, erythrocyte invasion, and hemoglobin degradation. Treatment with cysteine protease inhibitors blocks hemoglobin hydrolysis and development of the parasite. [4,[8][9][10][11][12] Both enzymes belong to the cathepsin L subfamily of the papain family of cysteine proteases.In a general protease-and cell-based screening using different proteases, we recently discovered hybrid compounds containing both a peptidic and a nonpeptidic moiety, namely a guanidinocarbonyl pyrrole, as potent inhibitors of falcipains with antiplasmodial activity (Scheme 1). The compounds were originally designed as new aspartic protease inhibitors but did not fulfill this expectation. However, the tert-butoxycarbonyl (Boc)-protected intermediates, for example, falcipain inhibitor A with a hybrid structure, unexpectedly displayed inhibitory activity against falcipains and plasmodia (FP-2: IC 50 = 3.1 mm; FP-3: no inhibition at 100 mm; P. f.: IC 50 = 1.7 mm). In order to evaluate which inhibitor fragment is responsible for the remarkable activity, the two building blocks B and C were tested individually. The peptidic fragment C was moderately active in the form of the ester (R = Et: FP-2: IC 50 = 34 mm; FP-3: IC 50 = 49 mm; P. f.: IC 50 = 29 mm; R= H: no inhibition at 100 mm); this was not unexpected, as Michael-acceptor-derived peptides have already been shown to be cysteine protease inhibitors. [13] However, to our surprise, the Boc-protected guanidinocarbonyl moiety B was also an efficient falcipain inhibitor (FP-2: IC 50 = 33 mm).Since preliminary docki...

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A Facile and Efficient Multi‐Gram Synthesis of N‐Protected 5‐(Guanidinocarbonyl)‐1H‐pyrrole‐2‐carboxylic Acids

Cited by 49 publications

References 25 publications

A New Chemosensing Ensemble for Colorimetric Detection of Oxalate in Water

A New Chemosensing Ensemble for Colorimetric Detection of Oxalate in Water

Downsizing of Enzymes by Chemical Methods: Arginine Mimics with Low pK_a Values Increase the Rates of Hydrolysis of RNA Model Compounds

Development of Antitrypanosomal and Antiplasmodial Nonpeptidic Cysteine Protease Inhibitors based on N‐Protected‐Guanidino‐Furan and ‐Pyrrole Building Blocks

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A Facile and Efficient Multi‐Gram Synthesis of N‐Protected 5‐(Guanidinocarbonyl)‐1H‐pyrrole‐2‐carboxylic Acids

Cited by 49 publications

References 25 publications

A New Chemosensing Ensemble for Colorimetric Detection of Oxalate in Water

A New Chemosensing Ensemble for Colorimetric Detection of Oxalate in Water

Downsizing of Enzymes by Chemical Methods: Arginine Mimics with Low pKa Values Increase the Rates of Hydrolysis of RNA Model Compounds

Development of Antitrypanosomal and Antiplasmodial Nonpeptidic Cysteine Protease Inhibitors based on N‐Protected‐Guanidino‐Furan and ‐Pyrrole Building Blocks

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Downsizing of Enzymes by Chemical Methods: Arginine Mimics with Low pK_a Values Increase the Rates of Hydrolysis of RNA Model Compounds