Carolina Burgos - Academia.edu (original) (raw)
Papers by Carolina Burgos
European Journal of Medicinal Chemistry, 2020
Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicit... more Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicity is a risk with overdose or in patients with compromised liver function. ApAP overdose is the most common cause of acute fulminant hepatic failure. Oxidation of ApAP to N-acetyl-p-benzoquinone imine (NAPQI) is the mechanism for hepatotoxicity. 1 is a non-hepatotoxic, metabolically unstable lipophilic ApAP analog that is not antipyretic. The newly synthesized 3 is a non-hepatotoxic ApAP analog that is stable, lipophilic, and retains analgesia and antipyresis. Intraperitoneal or po administration of the new chemical entities (NCEs), 3b and 3r, in concentrations equal to a toxic dose of ApAP did not result in the formation of NAPQI. Unlike livers from NCE-treated mice, the livers from ApAP-treated mice demonstrated large amounts of nitrotyrosine, a marker of mitochondrial free radical formation, and loss of hepatic tight junction integrity. Given the widespread use of ApAP, hepatotoxicity risk with overuse, and the ongoing opioid epidemic, these NCEs represent a novel, non-narcotic therapeutic pipeline.
RSC Advances, 2020
Results show that intramolecular radical [1,5]-ipso and [1,6]-ortho substitutions offer a method ... more Results show that intramolecular radical [1,5]-ipso and [1,6]-ortho substitutions offer a method for the preparation of aminobipyridines or bipyridine sultams.
Organic Chemistry Frontiers, 2019
A new method for the synthesis of 1-pyridin-3-yl-β-carboline derivatives involving an intramolecu... more A new method for the synthesis of 1-pyridin-3-yl-β-carboline derivatives involving an intramolecular radical reaction and SNAr substitution, is described.
European journal of medicinal chemistry, Jan 17, 2018
A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones were obtained a... more A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones were obtained and evaluated as calpain inhibitors. The hybrid compounds were inactive, whereas some members of the initial azolomethylideneimidazolone series showed interesting calpain inhibitory activity. By using 4b as a hit compound, a new series of analogs were synthesized by an efficient synthetic procedure based on a multicomponent reaction followed by an unprecedented reaction at the methylene position of the molecule. The best inhibitor found for calpain I (IC = 20 nM) was about 20 times more potent than the hit compound. Studies on 4b showed that its inhibition is consistent with an uncompetitive inhibition mode. This compound did not exhibit cellular toxicity at any of the doses tested (0.1-10 μM) and further studies indicated that it was capable of blockading chemical ischemia induction of apoptosis by preventing sodium azide-dependent calpain activation in intact human kidney tubular epithe...
European Journal of Organic Chemistry, 2016
The first example of a stable acylazinium salt obtained by an intramolecular acylpyridine-centere... more The first example of a stable acylazinium salt obtained by an intramolecular acylpyridine-centered radical attack on azine nitrogen atoms is reported. Depending on the relative position of the bromo substituent on the attacking amino-[a]
Organic Letters, 2014
A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of ... more A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of α-benzyl TosMIC derivatives has been developed. This methodology has been successfully applied to the total synthesis of mansouramycin B. This is the first total synthesis of this compound to be reported in the literature.
ChemInform, 2005
Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promote the intramolecular h... more Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promote the intramolecular heteroarylation of arenesulfonamides with pyridyl radicals under thermal conditions. The arenesulfonamides are easily prepared from pyridinium N-2 0pyridylaminide. The heteroarylation process involves pyridyl radical cyclization and ipso substitution.
Tetrahedron Letters, 2000
Pyridinium-N-(2 H-pyridyl)aminide was reacted with dierent a-halocarbonyl derivatives and related... more Pyridinium-N-(2 H-pyridyl)aminide was reacted with dierent a-halocarbonyl derivatives and related compounds. The method allows an easy preparation of several heterocyclic building blocks, all including the 2-aminopyridine moiety.
Tetrahedron Letters, 2008
A new total synthesis of the alkaloid variolin B is achieved by a selective and sequential pallad... more A new total synthesis of the alkaloid variolin B is achieved by a selective and sequential palladium-mediated functionalization of a trihalo-substituted pyrido[3 0 ,2 0 :4,5]pyrrolo[1,2-c]pyrimidine. This intermediate is obtained by a new heterocyclization reaction between an appropriate bromomethyl azaindole and N-tosylmethyl dichloroformimide. The methodology may be effective for the synthesis of some analogs by substitution on the relatively unexplored C4 and C9 positions of the alkaloid.
Tetrahedron Letters, 2007
A new and selective palladium-catalyzed amination of the pyrido[3 0 ,3 0 :4,5]pyrrolo[1,2-c]pyrim... more A new and selective palladium-catalyzed amination of the pyrido[3 0 ,3 0 :4,5]pyrrolo[1,2-c]pyrimidine nucleus, the heterocyclic core of the variolin alkaloids, is described. The method allows the introduction of amino and aryl-and alkylamino substituents on the C9 position in advanced precursors of variolin B and deoxyvariolin.
Tetrahedron, 2004
Tris(trimethylsilyl)silane (TTMSS) and azabisisobutyronitrile (AIBN) promoted the intermolecular ... more Tris(trimethylsilyl)silane (TTMSS) and azabisisobutyronitrile (AIBN) promoted the intermolecular arylation of aryl and heteroaryl bromides onto aromatic solvents under thermal conditions via a radical pathway.
Tetrahedron, 1995
The regioselective halogenatmn of pyrldmium-N-(2'-pyridyljaminide 1 with N-chloro, bromo or iodos... more The regioselective halogenatmn of pyrldmium-N-(2'-pyridyljaminide 1 with N-chloro, bromo or iodosuccinimtde under mild conditions IS described. The method, combined with a reductmn of the N-N bond, allows an easy preparation of 5-h& and 3,5-dihalo-Z-aminopyridines 4
Tetrahedron, 2007
The synthesis of benzonaphthyridine derivatives that incorporate a 2-aminopyridine moiety can be ... more The synthesis of benzonaphthyridine derivatives that incorporate a 2-aminopyridine moiety can be performed by intramolecular radical pyridylation of the appropriate substrates, obtained from pyridinium N-2 0-pyridylaminide, using TTMSS and AIBN.
Tetrahedron, 2013
ABSTRACT The synthesis of halogenated and arylated 1H-pyridin-2-ones starting from pyridinium N-(... more ABSTRACT The synthesis of halogenated and arylated 1H-pyridin-2-ones starting from pyridinium N-(pyridin-2-yl)aminides is described. The synthetic pathway involves the reaction of pyridinium N-(5-bromopyridin-2-yl)aminide, N-(3-bromo-5-chloropyridin-2-yl)aminide or N-(3,5-dibromopyridin-2-yl)aminide with different boronic acids to afford monosubstituted and disubstituted aminides in good yields. An additional bromination in the 3-position of N-(5-arylpyridin-2-yl)aminides was performed. Finally, reduction of the N–N bond followed by the reaction of the corresponding 2-aminopyridines with sodium nitrite/sulfuric acid in water yields 3,5-disubstituted 1H-pyridin-2-ones in good yields.
Organic Letters, 2000
Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promoted the easy intermolec... more Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promoted the easy intermolecular arylation of aryl and heteroaryl bromides under thermal conditions via a radical pathway.
Organic Letters, 2013
The reaction of alkyl tosylmethyl isocyanides and 2-bromobenzyl bromides in the presence of t-BuL... more The reaction of alkyl tosylmethyl isocyanides and 2-bromobenzyl bromides in the presence of t-BuLi gives rise to a cascade reaction to give unexpected 2-substituted 2,3-dihydro-1H-indenimines which, upon treatment with t-BuOK, rearrange to 2-vinylbenzonitriles in high overall yields. This simple procedure represents a new approach to the synthesis of aromatic nitriles via isocyanideÀcyanide interconversion.
The Journal of Organic Chemistry, 2008
The synthesis of dipyridopyrazole and pyridopyrazolopyrazine derivativessboth of which incorporat... more The synthesis of dipyridopyrazole and pyridopyrazolopyrazine derivativessboth of which incorporate a 3-aryl moietyscan be achieved in moderate yields by intramolecular radical arylation of pyridinium N-aminides using tris(trimethylsilyl)silane and azobisisobutyronitrile. Improved results were obtained on using Pd direct arylation in conjunction with microwave irradiation. A preliminary study into the fluorescent properties of the target compounds is also reported.
Journal of Molecular Structure, 1993
ABSTRACT
European Journal of Medicinal Chemistry, 2020
Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicit... more Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicity is a risk with overdose or in patients with compromised liver function. ApAP overdose is the most common cause of acute fulminant hepatic failure. Oxidation of ApAP to N-acetyl-p-benzoquinone imine (NAPQI) is the mechanism for hepatotoxicity. 1 is a non-hepatotoxic, metabolically unstable lipophilic ApAP analog that is not antipyretic. The newly synthesized 3 is a non-hepatotoxic ApAP analog that is stable, lipophilic, and retains analgesia and antipyresis. Intraperitoneal or po administration of the new chemical entities (NCEs), 3b and 3r, in concentrations equal to a toxic dose of ApAP did not result in the formation of NAPQI. Unlike livers from NCE-treated mice, the livers from ApAP-treated mice demonstrated large amounts of nitrotyrosine, a marker of mitochondrial free radical formation, and loss of hepatic tight junction integrity. Given the widespread use of ApAP, hepatotoxicity risk with overuse, and the ongoing opioid epidemic, these NCEs represent a novel, non-narcotic therapeutic pipeline.
RSC Advances, 2020
Results show that intramolecular radical [1,5]-ipso and [1,6]-ortho substitutions offer a method ... more Results show that intramolecular radical [1,5]-ipso and [1,6]-ortho substitutions offer a method for the preparation of aminobipyridines or bipyridine sultams.
Organic Chemistry Frontiers, 2019
A new method for the synthesis of 1-pyridin-3-yl-β-carboline derivatives involving an intramolecu... more A new method for the synthesis of 1-pyridin-3-yl-β-carboline derivatives involving an intramolecular radical reaction and SNAr substitution, is described.
European journal of medicinal chemistry, Jan 17, 2018
A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones were obtained a... more A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones were obtained and evaluated as calpain inhibitors. The hybrid compounds were inactive, whereas some members of the initial azolomethylideneimidazolone series showed interesting calpain inhibitory activity. By using 4b as a hit compound, a new series of analogs were synthesized by an efficient synthetic procedure based on a multicomponent reaction followed by an unprecedented reaction at the methylene position of the molecule. The best inhibitor found for calpain I (IC = 20 nM) was about 20 times more potent than the hit compound. Studies on 4b showed that its inhibition is consistent with an uncompetitive inhibition mode. This compound did not exhibit cellular toxicity at any of the doses tested (0.1-10 μM) and further studies indicated that it was capable of blockading chemical ischemia induction of apoptosis by preventing sodium azide-dependent calpain activation in intact human kidney tubular epithe...
European Journal of Organic Chemistry, 2016
The first example of a stable acylazinium salt obtained by an intramolecular acylpyridine-centere... more The first example of a stable acylazinium salt obtained by an intramolecular acylpyridine-centered radical attack on azine nitrogen atoms is reported. Depending on the relative position of the bromo substituent on the attacking amino-[a]
Organic Letters, 2014
A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of ... more A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of α-benzyl TosMIC derivatives has been developed. This methodology has been successfully applied to the total synthesis of mansouramycin B. This is the first total synthesis of this compound to be reported in the literature.
ChemInform, 2005
Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promote the intramolecular h... more Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promote the intramolecular heteroarylation of arenesulfonamides with pyridyl radicals under thermal conditions. The arenesulfonamides are easily prepared from pyridinium N-2 0pyridylaminide. The heteroarylation process involves pyridyl radical cyclization and ipso substitution.
Tetrahedron Letters, 2000
Pyridinium-N-(2 H-pyridyl)aminide was reacted with dierent a-halocarbonyl derivatives and related... more Pyridinium-N-(2 H-pyridyl)aminide was reacted with dierent a-halocarbonyl derivatives and related compounds. The method allows an easy preparation of several heterocyclic building blocks, all including the 2-aminopyridine moiety.
Tetrahedron Letters, 2008
A new total synthesis of the alkaloid variolin B is achieved by a selective and sequential pallad... more A new total synthesis of the alkaloid variolin B is achieved by a selective and sequential palladium-mediated functionalization of a trihalo-substituted pyrido[3 0 ,2 0 :4,5]pyrrolo[1,2-c]pyrimidine. This intermediate is obtained by a new heterocyclization reaction between an appropriate bromomethyl azaindole and N-tosylmethyl dichloroformimide. The methodology may be effective for the synthesis of some analogs by substitution on the relatively unexplored C4 and C9 positions of the alkaloid.
Tetrahedron Letters, 2007
A new and selective palladium-catalyzed amination of the pyrido[3 0 ,3 0 :4,5]pyrrolo[1,2-c]pyrim... more A new and selective palladium-catalyzed amination of the pyrido[3 0 ,3 0 :4,5]pyrrolo[1,2-c]pyrimidine nucleus, the heterocyclic core of the variolin alkaloids, is described. The method allows the introduction of amino and aryl-and alkylamino substituents on the C9 position in advanced precursors of variolin B and deoxyvariolin.
Tetrahedron, 2004
Tris(trimethylsilyl)silane (TTMSS) and azabisisobutyronitrile (AIBN) promoted the intermolecular ... more Tris(trimethylsilyl)silane (TTMSS) and azabisisobutyronitrile (AIBN) promoted the intermolecular arylation of aryl and heteroaryl bromides onto aromatic solvents under thermal conditions via a radical pathway.
Tetrahedron, 1995
The regioselective halogenatmn of pyrldmium-N-(2'-pyridyljaminide 1 with N-chloro, bromo or iodos... more The regioselective halogenatmn of pyrldmium-N-(2'-pyridyljaminide 1 with N-chloro, bromo or iodosuccinimtde under mild conditions IS described. The method, combined with a reductmn of the N-N bond, allows an easy preparation of 5-h& and 3,5-dihalo-Z-aminopyridines 4
Tetrahedron, 2007
The synthesis of benzonaphthyridine derivatives that incorporate a 2-aminopyridine moiety can be ... more The synthesis of benzonaphthyridine derivatives that incorporate a 2-aminopyridine moiety can be performed by intramolecular radical pyridylation of the appropriate substrates, obtained from pyridinium N-2 0-pyridylaminide, using TTMSS and AIBN.
Tetrahedron, 2013
ABSTRACT The synthesis of halogenated and arylated 1H-pyridin-2-ones starting from pyridinium N-(... more ABSTRACT The synthesis of halogenated and arylated 1H-pyridin-2-ones starting from pyridinium N-(pyridin-2-yl)aminides is described. The synthetic pathway involves the reaction of pyridinium N-(5-bromopyridin-2-yl)aminide, N-(3-bromo-5-chloropyridin-2-yl)aminide or N-(3,5-dibromopyridin-2-yl)aminide with different boronic acids to afford monosubstituted and disubstituted aminides in good yields. An additional bromination in the 3-position of N-(5-arylpyridin-2-yl)aminides was performed. Finally, reduction of the N–N bond followed by the reaction of the corresponding 2-aminopyridines with sodium nitrite/sulfuric acid in water yields 3,5-disubstituted 1H-pyridin-2-ones in good yields.
Organic Letters, 2000
Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promoted the easy intermolec... more Tris(trimethylsilyl)silane (TTMSS) and azobisisobutironitrile (AIBN) promoted the easy intermolecular arylation of aryl and heteroaryl bromides under thermal conditions via a radical pathway.
Organic Letters, 2013
The reaction of alkyl tosylmethyl isocyanides and 2-bromobenzyl bromides in the presence of t-BuL... more The reaction of alkyl tosylmethyl isocyanides and 2-bromobenzyl bromides in the presence of t-BuLi gives rise to a cascade reaction to give unexpected 2-substituted 2,3-dihydro-1H-indenimines which, upon treatment with t-BuOK, rearrange to 2-vinylbenzonitriles in high overall yields. This simple procedure represents a new approach to the synthesis of aromatic nitriles via isocyanideÀcyanide interconversion.
The Journal of Organic Chemistry, 2008
The synthesis of dipyridopyrazole and pyridopyrazolopyrazine derivativessboth of which incorporat... more The synthesis of dipyridopyrazole and pyridopyrazolopyrazine derivativessboth of which incorporate a 3-aryl moietyscan be achieved in moderate yields by intramolecular radical arylation of pyridinium N-aminides using tris(trimethylsilyl)silane and azobisisobutyronitrile. Improved results were obtained on using Pd direct arylation in conjunction with microwave irradiation. A preliminary study into the fluorescent properties of the target compounds is also reported.
Journal of Molecular Structure, 1993
ABSTRACT