Edward Turos - Academia.edu (original) (raw)
Papers by Edward Turos
ChemInform, 1996
1996 ring closure reactions ring closure reactions O 0130
A study on the structure-activity profiles of N-thiolated b-lactams 1 is reported which demonstra... more A study on the structure-activity profiles of N-thiolated b-lactams 1 is reported which demonstrates the importance of the N-organothio moiety on antibacterial activity. Our results indicate that elongation of the N-alkylthio residue beyond two carbons, or extensive branching within the organothio substituent, diminishes antibacterial effects. Of the derivatives we examined, the N-sec-butylthio b-lactam derivative 5g possesses the strongest growth inhibitory activity against methicillin-resistant Staphylococcus aureus strains. Sulfur oxidation state is important, as the N-sulfenyl and N-sulfinyl groups provide for the best antibacterial activity, while lactams bearing the N-sulfonyl or N-sulfonic acid functionalities have much weaker or no anti-MRSA properties. Stereochemistry within the organothio chain does not seem to be a significant factor, although for N-sec-butylthio b-lactams 15a-d, the 3R,4S-lactams 15c, d are more active than the 3S,4R-stereoisomers 15a, b in agar diffusion experiments. The N-methylthio lactams are the most sensitive to the presence of glutathione, followed by N-ethylthio and N-sec-butylthio lactams, which indicates that bioactivity and perhaps bacterial selectivity of the lactams may be related to the amount of organothiols in the bacterial cell. These results support the empirical model for the mechanism of action of the compounds in which the lactam transverses the bacterial membrane to deliver the organothio moiety to its cellular target.
Journal of Organic Chemistry, 1998
Described in this article are studies of structurally novel [3.2. 0] bicyclic β-lactam ring syste... more Described in this article are studies of structurally novel [3.2. 0] bicyclic β-lactam ring systems that are isomeric to those of the penicillin, penem, and clavulanic acid families of antibiotics, but which have the lactam functionality arranged in alternative orientations ...
Tetrahedron: Asymmetry, 2009
... Auteur(s) / Author(s). PEREZ SANCHEZ Ivan ; TUROS Edward ; ... These glycosylated adducts und... more ... Auteur(s) / Author(s). PEREZ SANCHEZ Ivan ; TUROS Edward ; ... These glycosylated adducts undergo hetero-Diels-Alder reactions with 2-formyl-l-malondialdehyde to afford 2',5'- dideoxygenated disaccharides in good yields and complete regio-and endo-selectivity. ...
Tetrahedron, 2000
AbstractÐIn this study, we describe the synthesis and features of b-lactam ring systems having an... more AbstractÐIn this study, we describe the synthesis and features of b-lactam ring systems having an alkylthio substituent on the lactam nitrogen center. The sulfur group acts to enhance the electrophilic character of the lactam carbonyl through electron withdrawal, and in bicyclic systems, reduces pyramidalization of the nitrogen center. Despite their electrophilic nature, these ring systems are chemically stable towards hydrolysis in aqueous media, but can be cleaved at the N±S bond by reducing agents such as triphenylphosphine. N-Methylthio substituted lactams favor a conformation having the sulfur±carbon bond of the SMe group aligned orthogonally with respect to the ring, with a facile interconversion between the cis and trans rotamers. These N-methylthio substituted lactams show potent antimicrobial behavior towards Staphylococcus aureus, including drug-resistant forms, and are not hydrolyzed by b-lactamases. From the data presented, there is a strong suggestion that these lactams may operate through a chemical and biological mechanism of action that is different from all previous classes of b-lactam drugs. q
Tetrahedron Letters, 1992
... 47, O. 70937096,1992 O040O39 92 55.00+.00 Printed in Great Britain Pergamon Press Ltd Halogen... more ... 47, O. 70937096,1992 O040O39 92 55.00+.00 Printed in Great Britain Pergamon Press Ltd Halogenation Reactions of Epoxides Monica I. Konaklieva, Michele L. Dahl, and Edward Turos' Department of Chemistry State University of New York at ... (b) J. Rodriquez; JP Dulcere; M ...
Tetrahedron, 2003
Pseudomonas cepacia lipase (PS-30) was used in hydrolytic resolution of 3-acetoxy-4-aryl-substitu... more Pseudomonas cepacia lipase (PS-30) was used in hydrolytic resolution of 3-acetoxy-4-aryl-substituted azetidin-2-ones (.97% ee). Twenty-three b-lactam substrates with varied substituents at the C-4 center of the ring were synthesized and subjected to lipase-PS catalyzed hydrolysis in phosphate buffer (pH 7.2, 0.2 M) at 258C. The reactions occurred with high enantioselectivity and substrate conversion. The effect of substitution on the C-4 aryl ring on lipase hydrolytic activity was dependent upon the steric and electronic nature of the substituent and its position on the aryl ring. The stereopreference of the lipase PS-30 for the (3S,4R) enantiomer was rationalized using a known active site model. Absolute stereochemistry of the enantiomers was established using single crystal X-ray crystallographic techniques. q
Synthetic Communications, 1982
A convenient method has been developed for directly converting esters to amides using reagents de... more A convenient method has been developed for directly converting esters to amides using reagents derived from the reaction of trimethylaluminum with ammonium chloride, methylamine hydrochloride or dimethylamine hydrochloride.
Organic Letters, 2007
The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxa... more The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxazolidinones, is described for the first time. In this approach, 2-oxazolidinones are prepared in stereomerically pure form from 3-hydroxy beta-lactams by a ring-opening-cyclization isomerization process. Application of this methodology to the total synthesis of the cytokine modulator, (-)-cytoxazone, and its three stereoisomers is demonstrated. [reaction: see text].
Nanomedicine: Nanotechnology, Biology and Medicine, 2008
Recent research in our laboratory has centered on studies of polyacrylate and polyacrylamide nano... more Recent research in our laboratory has centered on studies of polyacrylate and polyacrylamide nanoparticle emulsions for use in antibiotic delivery. Our goal is to develop these nanoparticle emulsions for treatment of life-threatening bacterial infections such as those caused by methicillinresistant Staphylococcus aureus. For this intended application it is necessary to ensure that the biological activity of the emulsion is due only to the drug attached to the polymeric chain and not to any extraneous components. To investigate this we evaluated cytotoxicity and microbiological activity of the nanoparticle emulsions before and after purification by centrifugation, dialysis, and gel filtration. Depending on the amount of surfactant used, all or most of the microbial and cellular toxicity can be removed by a simple purification procedure. Methods for purifying and detoxifying sodium dodecyl sulfate-stabilized polyacrylate nanoparticles. Nanomedicine: NBM 2008;4:98-105,
Nanomedicine: Nanotechnology, Biology and Medicine, 2009
We have recently reported on a new nanomedicine containing antibiotic-conjugated polyacrylate nan... more We have recently reported on a new nanomedicine containing antibiotic-conjugated polyacrylate nanoparticles, which has shown activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and no cytotoxicity toward human dermal cells. The water-based nanoparticle emulsion is capable of solubilizing lipophilic antibiotics for systemic administration, and the nanoparticle drug delivery vehicle has shown protective properties for antibiotics from hydrolytic cleavage by bacterial penicillinases, thus rejuvenating the drug's activity against resistant microbes such as MRSA. Here we report the first in vivo study of this penicillin-conjugated nanoparticle emulsion in determining toxicological responses initiated upon systemic and topical application in a murine model. Favorable results were observed in vivo upon both routes of administration and, when topically applied to a dermal abrasion model, the emulsion enhanced wound healing by an average of 3 to 5 days. This study suggests that polyacrylate nanoparticle-containing emulsions may afford promising opportunities for treating both skin and systemic infections.
Nanomedicine: Nanotechnology, Biology and Medicine, 2009
Recent efforts in our laboratory have explored the use of polyacrylate nanoparticles in aqueous m... more Recent efforts in our laboratory have explored the use of polyacrylate nanoparticles in aqueous media as stable emulsions for potential applications in treating drug-resistant bacterial infections. These emulsions are made by emulsion polymerization of acrylated antibiotic compounds in a mixture of butyl acrylate and styrene (7:3 wt/wt) using sodium dodecyl sulfate as a surfactant. Prior work in our group established that the emulsions required purification to remove toxicity associated with extraneous surfactant present in the media. This article summarizes our investigations of poly(butyl acrylate-styrene) emulsions made using anionic, cationic, zwitterionic, and noncharged (amphiphilic) surfactants, as well as attachable surfactant monomers (surfmers), comparing the cytotoxicity and microbiological activity levels of the emulsion both before and after purification. Our results show that the attachment of a polymerizable surfmer onto the matrix of the nanoparticle neither improves nor diminishes cytotoxic or antibacterial effects of the emulsion, whether or not the emulsions are purified, and that the optimal properties are associated with the use of the nonionic surfactants versus those carrying anionic, cationic, or zwitterionic charge. Incorporation of an N-thiolated beta-lactam antibacterial agent onto the nanoparticle matrix via covalent attachment endows the emulsion with antibiotic properties against pathogenic bacteria such as methicillin-resistant Staphylococcus aureus, without changing the physical properties of the nanoparticles or their emulsions. Emulsions of polyacrylate nanoparticles, antibiotics and surfactants were studied using surfactant monomers as controls. Nonionic surfactants resulted in the most optimal properties. Incorporation of a beta-lactam antibacterial agent onto the nanoparticle matrix endowed the emulsion with antibiotic properties against methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of hospital acquired, treatment-resistant infections including sepsis.
Journal of the American Chemical Society, 1989
... (1) (a) Wray, BB; O'Steen, KG Arch. Enuiron. Health 1975, 30, 571. (b) Wray, B. 9.; ... more ... (1) (a) Wray, BB; O'Steen, KG Arch. Enuiron. Health 1975, 30, 571. (b) Wray, B. 9.; Rushing, E. J.; Boyd, R.; Schindel, AM Arch. Enuiron. ... Agents Chemother. 1974,5,634. (b) Vesonder, RF; Tjarks, LW; Rohwedder, WK; Burmeister, HR; Laugal, J. A. J . Antibiot. 1979, 32, 759. ...
Journal of Organometallic Chemistry, 2001
The Journal of Organic Chemistry, 1984
... David M. Tschaen, Edward Turos, and Steven M. Weinreb ... either thermal or Lewis acid mediat... more ... David M. Tschaen, Edward Turos, and Steven M. Weinreb ... either thermal or Lewis acid mediated intramolecular ene reaction and that the corresponding prenyl system gave a low yield of a 1:l mixture of exo and endo products.s Glyoxylate 26c, derived from (E)-3-hexen-l-ol, was ...
The Journal of Organic Chemistry, 1995
Our laboratory has become interested in the design and synthesis of bicyclic p-lactam ring system... more Our laboratory has become interested in the design and synthesis of bicyclic p-lactam ring systems whose novel structures might provide useful leads in the search for new antibacterial agents.l We recently described the synthesis of two such classes of structures related to the classical penamor penem-ring systems in which the lactam is adjacent to, but not directly part of, the ring f~s i o n .~,~ In this paper, we report the synthesis of a second class of p-lactam core structures 1 and 2 that closely resemble those of the penems and clavulanic acids, except that the orientation of the lactam group has formally been inverted with respect to the thiazolidine ring, producing an effect that enhances the electrophilicity of the azetidinone ring. X 1 OR' 2
The Journal of Organic Chemistry, 1994
... SOC., Chem. Commun. 1977, 748. (8) (a) Narisada, M.; Yoshida, T.; Onoue, H.; Ohani, M.; Okada... more ... SOC., Chem. Commun. 1977, 748. (8) (a) Narisada, M.; Yoshida, T.; Onoue, H.; Ohani, M.; Okada, T.; Tsuji, T.; Kikkana, I.; Haga, N.; Satoh, H.; Itani, H.; Nagata, W. J. Med. Chem. 1979,22, 757. ... SOC., Perkin Trans. 2 1982, 1185. (h) Sheehan, JC; Ryan, JJ J. Am. Chem. SOC. ...
ChemInform, 1996
1996 ring closure reactions ring closure reactions O 0130
A study on the structure-activity profiles of N-thiolated b-lactams 1 is reported which demonstra... more A study on the structure-activity profiles of N-thiolated b-lactams 1 is reported which demonstrates the importance of the N-organothio moiety on antibacterial activity. Our results indicate that elongation of the N-alkylthio residue beyond two carbons, or extensive branching within the organothio substituent, diminishes antibacterial effects. Of the derivatives we examined, the N-sec-butylthio b-lactam derivative 5g possesses the strongest growth inhibitory activity against methicillin-resistant Staphylococcus aureus strains. Sulfur oxidation state is important, as the N-sulfenyl and N-sulfinyl groups provide for the best antibacterial activity, while lactams bearing the N-sulfonyl or N-sulfonic acid functionalities have much weaker or no anti-MRSA properties. Stereochemistry within the organothio chain does not seem to be a significant factor, although for N-sec-butylthio b-lactams 15a-d, the 3R,4S-lactams 15c, d are more active than the 3S,4R-stereoisomers 15a, b in agar diffusion experiments. The N-methylthio lactams are the most sensitive to the presence of glutathione, followed by N-ethylthio and N-sec-butylthio lactams, which indicates that bioactivity and perhaps bacterial selectivity of the lactams may be related to the amount of organothiols in the bacterial cell. These results support the empirical model for the mechanism of action of the compounds in which the lactam transverses the bacterial membrane to deliver the organothio moiety to its cellular target.
Journal of Organic Chemistry, 1998
Described in this article are studies of structurally novel [3.2. 0] bicyclic β-lactam ring syste... more Described in this article are studies of structurally novel [3.2. 0] bicyclic β-lactam ring systems that are isomeric to those of the penicillin, penem, and clavulanic acid families of antibiotics, but which have the lactam functionality arranged in alternative orientations ...
Tetrahedron: Asymmetry, 2009
... Auteur(s) / Author(s). PEREZ SANCHEZ Ivan ; TUROS Edward ; ... These glycosylated adducts und... more ... Auteur(s) / Author(s). PEREZ SANCHEZ Ivan ; TUROS Edward ; ... These glycosylated adducts undergo hetero-Diels-Alder reactions with 2-formyl-l-malondialdehyde to afford 2',5'- dideoxygenated disaccharides in good yields and complete regio-and endo-selectivity. ...
Tetrahedron, 2000
AbstractÐIn this study, we describe the synthesis and features of b-lactam ring systems having an... more AbstractÐIn this study, we describe the synthesis and features of b-lactam ring systems having an alkylthio substituent on the lactam nitrogen center. The sulfur group acts to enhance the electrophilic character of the lactam carbonyl through electron withdrawal, and in bicyclic systems, reduces pyramidalization of the nitrogen center. Despite their electrophilic nature, these ring systems are chemically stable towards hydrolysis in aqueous media, but can be cleaved at the N±S bond by reducing agents such as triphenylphosphine. N-Methylthio substituted lactams favor a conformation having the sulfur±carbon bond of the SMe group aligned orthogonally with respect to the ring, with a facile interconversion between the cis and trans rotamers. These N-methylthio substituted lactams show potent antimicrobial behavior towards Staphylococcus aureus, including drug-resistant forms, and are not hydrolyzed by b-lactamases. From the data presented, there is a strong suggestion that these lactams may operate through a chemical and biological mechanism of action that is different from all previous classes of b-lactam drugs. q
Tetrahedron Letters, 1992
... 47, O. 70937096,1992 O040O39 92 55.00+.00 Printed in Great Britain Pergamon Press Ltd Halogen... more ... 47, O. 70937096,1992 O040O39 92 55.00+.00 Printed in Great Britain Pergamon Press Ltd Halogenation Reactions of Epoxides Monica I. Konaklieva, Michele L. Dahl, and Edward Turos' Department of Chemistry State University of New York at ... (b) J. Rodriquez; JP Dulcere; M ...
Tetrahedron, 2003
Pseudomonas cepacia lipase (PS-30) was used in hydrolytic resolution of 3-acetoxy-4-aryl-substitu... more Pseudomonas cepacia lipase (PS-30) was used in hydrolytic resolution of 3-acetoxy-4-aryl-substituted azetidin-2-ones (.97% ee). Twenty-three b-lactam substrates with varied substituents at the C-4 center of the ring were synthesized and subjected to lipase-PS catalyzed hydrolysis in phosphate buffer (pH 7.2, 0.2 M) at 258C. The reactions occurred with high enantioselectivity and substrate conversion. The effect of substitution on the C-4 aryl ring on lipase hydrolytic activity was dependent upon the steric and electronic nature of the substituent and its position on the aryl ring. The stereopreference of the lipase PS-30 for the (3S,4R) enantiomer was rationalized using a known active site model. Absolute stereochemistry of the enantiomers was established using single crystal X-ray crystallographic techniques. q
Synthetic Communications, 1982
A convenient method has been developed for directly converting esters to amides using reagents de... more A convenient method has been developed for directly converting esters to amides using reagents derived from the reaction of trimethylaluminum with ammonium chloride, methylamine hydrochloride or dimethylamine hydrochloride.
Organic Letters, 2007
The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxa... more The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxazolidinones, is described for the first time. In this approach, 2-oxazolidinones are prepared in stereomerically pure form from 3-hydroxy beta-lactams by a ring-opening-cyclization isomerization process. Application of this methodology to the total synthesis of the cytokine modulator, (-)-cytoxazone, and its three stereoisomers is demonstrated. [reaction: see text].
Nanomedicine: Nanotechnology, Biology and Medicine, 2008
Recent research in our laboratory has centered on studies of polyacrylate and polyacrylamide nano... more Recent research in our laboratory has centered on studies of polyacrylate and polyacrylamide nanoparticle emulsions for use in antibiotic delivery. Our goal is to develop these nanoparticle emulsions for treatment of life-threatening bacterial infections such as those caused by methicillinresistant Staphylococcus aureus. For this intended application it is necessary to ensure that the biological activity of the emulsion is due only to the drug attached to the polymeric chain and not to any extraneous components. To investigate this we evaluated cytotoxicity and microbiological activity of the nanoparticle emulsions before and after purification by centrifugation, dialysis, and gel filtration. Depending on the amount of surfactant used, all or most of the microbial and cellular toxicity can be removed by a simple purification procedure. Methods for purifying and detoxifying sodium dodecyl sulfate-stabilized polyacrylate nanoparticles. Nanomedicine: NBM 2008;4:98-105,
Nanomedicine: Nanotechnology, Biology and Medicine, 2009
We have recently reported on a new nanomedicine containing antibiotic-conjugated polyacrylate nan... more We have recently reported on a new nanomedicine containing antibiotic-conjugated polyacrylate nanoparticles, which has shown activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and no cytotoxicity toward human dermal cells. The water-based nanoparticle emulsion is capable of solubilizing lipophilic antibiotics for systemic administration, and the nanoparticle drug delivery vehicle has shown protective properties for antibiotics from hydrolytic cleavage by bacterial penicillinases, thus rejuvenating the drug's activity against resistant microbes such as MRSA. Here we report the first in vivo study of this penicillin-conjugated nanoparticle emulsion in determining toxicological responses initiated upon systemic and topical application in a murine model. Favorable results were observed in vivo upon both routes of administration and, when topically applied to a dermal abrasion model, the emulsion enhanced wound healing by an average of 3 to 5 days. This study suggests that polyacrylate nanoparticle-containing emulsions may afford promising opportunities for treating both skin and systemic infections.
Nanomedicine: Nanotechnology, Biology and Medicine, 2009
Recent efforts in our laboratory have explored the use of polyacrylate nanoparticles in aqueous m... more Recent efforts in our laboratory have explored the use of polyacrylate nanoparticles in aqueous media as stable emulsions for potential applications in treating drug-resistant bacterial infections. These emulsions are made by emulsion polymerization of acrylated antibiotic compounds in a mixture of butyl acrylate and styrene (7:3 wt/wt) using sodium dodecyl sulfate as a surfactant. Prior work in our group established that the emulsions required purification to remove toxicity associated with extraneous surfactant present in the media. This article summarizes our investigations of poly(butyl acrylate-styrene) emulsions made using anionic, cationic, zwitterionic, and noncharged (amphiphilic) surfactants, as well as attachable surfactant monomers (surfmers), comparing the cytotoxicity and microbiological activity levels of the emulsion both before and after purification. Our results show that the attachment of a polymerizable surfmer onto the matrix of the nanoparticle neither improves nor diminishes cytotoxic or antibacterial effects of the emulsion, whether or not the emulsions are purified, and that the optimal properties are associated with the use of the nonionic surfactants versus those carrying anionic, cationic, or zwitterionic charge. Incorporation of an N-thiolated beta-lactam antibacterial agent onto the nanoparticle matrix via covalent attachment endows the emulsion with antibiotic properties against pathogenic bacteria such as methicillin-resistant Staphylococcus aureus, without changing the physical properties of the nanoparticles or their emulsions. Emulsions of polyacrylate nanoparticles, antibiotics and surfactants were studied using surfactant monomers as controls. Nonionic surfactants resulted in the most optimal properties. Incorporation of a beta-lactam antibacterial agent onto the nanoparticle matrix endowed the emulsion with antibiotic properties against methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of hospital acquired, treatment-resistant infections including sepsis.
Journal of the American Chemical Society, 1989
... (1) (a) Wray, BB; O'Steen, KG Arch. Enuiron. Health 1975, 30, 571. (b) Wray, B. 9.; ... more ... (1) (a) Wray, BB; O'Steen, KG Arch. Enuiron. Health 1975, 30, 571. (b) Wray, B. 9.; Rushing, E. J.; Boyd, R.; Schindel, AM Arch. Enuiron. ... Agents Chemother. 1974,5,634. (b) Vesonder, RF; Tjarks, LW; Rohwedder, WK; Burmeister, HR; Laugal, J. A. J . Antibiot. 1979, 32, 759. ...
Journal of Organometallic Chemistry, 2001
The Journal of Organic Chemistry, 1984
... David M. Tschaen, Edward Turos, and Steven M. Weinreb ... either thermal or Lewis acid mediat... more ... David M. Tschaen, Edward Turos, and Steven M. Weinreb ... either thermal or Lewis acid mediated intramolecular ene reaction and that the corresponding prenyl system gave a low yield of a 1:l mixture of exo and endo products.s Glyoxylate 26c, derived from (E)-3-hexen-l-ol, was ...
The Journal of Organic Chemistry, 1995
Our laboratory has become interested in the design and synthesis of bicyclic p-lactam ring system... more Our laboratory has become interested in the design and synthesis of bicyclic p-lactam ring systems whose novel structures might provide useful leads in the search for new antibacterial agents.l We recently described the synthesis of two such classes of structures related to the classical penamor penem-ring systems in which the lactam is adjacent to, but not directly part of, the ring f~s i o n .~,~ In this paper, we report the synthesis of a second class of p-lactam core structures 1 and 2 that closely resemble those of the penems and clavulanic acids, except that the orientation of the lactam group has formally been inverted with respect to the thiazolidine ring, producing an effect that enhances the electrophilicity of the azetidinone ring. X 1 OR' 2
The Journal of Organic Chemistry, 1994
... SOC., Chem. Commun. 1977, 748. (8) (a) Narisada, M.; Yoshida, T.; Onoue, H.; Ohani, M.; Okada... more ... SOC., Chem. Commun. 1977, 748. (8) (a) Narisada, M.; Yoshida, T.; Onoue, H.; Ohani, M.; Okada, T.; Tsuji, T.; Kikkana, I.; Haga, N.; Satoh, H.; Itani, H.; Nagata, W. J. Med. Chem. 1979,22, 757. ... SOC., Perkin Trans. 2 1982, 1185. (h) Sheehan, JC; Ryan, JJ J. Am. Chem. SOC. ...