The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Wengsang Huang - One of the best experts on this subject based on the ideXlab platform.
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synthesis of chiral furopyrrolizidinones through a key tandem cope elimination 1 3 dipolar cycloaddition reaction of tricyclic lactones
ChemInform, 2011Co-Authors: Hsiangyu Chuang, Shangming Yeh, Wengsang HuangAbstract:The highly functionalized title compounds (III) containing contiguous quarternary centers are synthesized by oxidation of the tricyclic compounds (I) with MCPBA under basic conditions through a tandem Cope elimination/1,3-dipolar cycloaddition sequence followed by reduction of (II) inducing N—O cleavage and Lactam Ring cyclization.
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synthesis of chiral furopyrrolizidinones through a key tandem cope elimination 1 3 dipolar cycloaddition reaction of tricyclic lactones
European Journal of Organic Chemistry, 2011Co-Authors: Hsiangyu Chuang, Shangming Yeh, Wengsang HuangAbstract:Highly functionalized chiral furo-pyrrolizidinones containing contiguous quaternary centers were synthesized in moderate to good yields by treatment of various hexahydro-3,4-dioxa-8a-aza-as-indacen-2-ones with m-CPBA under basic conditions through a tandem Cope elimination/1,3-dipolar cycloaddition reaction sequence, followed by N-O cleavage and Lactam Ring cyclization.
Craig A Townsend - One of the best experts on this subject based on the ideXlab platform.
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monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase
Nature Chemical Biology, 2018Co-Authors: Ryan A Oliver, Craig A TownsendAbstract:Biosynthesis of the antibiotic sulfazecin involves N-sulfonation in trans of the tripeptide intermediate before synthesis of the β-Lactam Ring by a noncanonical thioesterase domain, demonstrating a new enzymatic route to the azetidinone moiety.
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epimerization and substrate gating by a te domain in β Lactam antibiotic biosynthesis
Nature Chemical Biology, 2014Co-Authors: Nicole M Gaudelli, Craig A TownsendAbstract:Synthetic analogs of nocardicin G—a key precursor of β-Lactam antibiotics—are used to show that construction of this enigmatic modified tripeptide relies on an unusual thioesterase domain that epimerizes one residue of an intermediate pentapeptide, but only when the Lactam Ring is already formed.
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rate limiting steps and role of active site lys443 in the mechanism of carbapenam synthetase
Biochemistry, 2007Co-Authors: Samantha O Arnett, Barbara Gerratana, Craig A TownsendAbstract:Carbapenam synthetase (hereafter named CPS) catalyzes the formation of the β-Lactam Ring in the biosynthetic pathway to (5R)-carbapen-2-em-3-carboxylate, the simplest of the carbapenem antibiotics. Kinetic studies showed remarkable tolerance to substrate stereochemistry in the turnover rate but did not distinguish between chemistry and a nonchemical step such as product release or conformational change as being rate-determining. Also, X-ray structural studies and modest sequence homology to β-Lactam synthetase, an enzyme that catalyzes the formation of a monocyclic β-Lactam Ring in a similar ATP/Mg2+-dependent reaction, implicate K443 as an essential residue for substrate binding and intermediate stabilization. In these experiments, we use pH−rate profiles, deuterium solvent isotope effects, and solvent viscosity measurements to examine the rate-limiting step in this complex overall process of substrate adenylation and intramolecular Ring formation. Mutagenesis and chemical rescue demonstrate that K443 is...
Hsiangyu Chuang - One of the best experts on this subject based on the ideXlab platform.
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synthesis of chiral furopyrrolizidinones through a key tandem cope elimination 1 3 dipolar cycloaddition reaction of tricyclic lactones
ChemInform, 2011Co-Authors: Hsiangyu Chuang, Shangming Yeh, Wengsang HuangAbstract:The highly functionalized title compounds (III) containing contiguous quarternary centers are synthesized by oxidation of the tricyclic compounds (I) with MCPBA under basic conditions through a tandem Cope elimination/1,3-dipolar cycloaddition sequence followed by reduction of (II) inducing N—O cleavage and Lactam Ring cyclization.
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synthesis of chiral furopyrrolizidinones through a key tandem cope elimination 1 3 dipolar cycloaddition reaction of tricyclic lactones
European Journal of Organic Chemistry, 2011Co-Authors: Hsiangyu Chuang, Shangming Yeh, Wengsang HuangAbstract:Highly functionalized chiral furo-pyrrolizidinones containing contiguous quaternary centers were synthesized in moderate to good yields by treatment of various hexahydro-3,4-dioxa-8a-aza-as-indacen-2-ones with m-CPBA under basic conditions through a tandem Cope elimination/1,3-dipolar cycloaddition reaction sequence, followed by N-O cleavage and Lactam Ring cyclization.
Ying Dong - One of the best experts on this subject based on the ideXlab platform.
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pyrrole strategy for the γ Lactam containing stemona alkaloids stemoamide tuberostemoamide and sessilifoliamide a
Organic Letters, 2020Co-Authors: Ying DongAbstract:Stemona alkaloids contain family members with diverse structural scaffolds. Many of them feature a γ-Lactam Ring embedded in their characteristic 5–7–5 fused tricyclic core. Herein a pyrrole strate...
Edward Turos - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and biological evaluation of some novel diastereoselective benzothiazole beta-Lactam conjugates
European Journal of Medicinal Chemistry, 2018Co-Authors: Maryam Alborz, Aliasghar Jarrahpour, Roya Pournejati, Hamid Reza Karbalaei-heidari, Veronique Sinou, Christine Latour, Jean Michel Brunel, Hashem Sharghi, Mandi Aberi, Edward TurosAbstract:Highly diastereoselective synthesis of some novel benzothiazole-substituted beta-Lactam hybrids was achieved starting from (benzo[d]thiazol-2-yl)phenol as an available precursor. This is the first time (benzo[d]thiazol-2-yl)phenoxyacetic acid has been used as ketene source in synthesizing monocyclic 2-azetidinones. These compounds were evaluated for their antimicrobial activities against a large panel of Gram-positive and Gram-negative bacterial strains and moderate activities were encountered. Antimalarial data revealed that adding methoxyphenyl or ethoxyphenyl group on the beta-Lactam Ring makes compounds that are more potent. Moreover, hemolytic activity and mammalian cell toxicity survey of the compounds showed their potential as a medicine. (C) 2017 Elsevier Masson SAS. All rights reserved.
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induction of tumor cell apoptosis by a novel class of n thiolated β Lactam antibiotics with structural modifications at n1 and c3 of the Lactam Ring
International Journal of Molecular Medicine, 2008Co-Authors: Michael Frezza, Edward Turos, Julio Garay, Di Chen, Cindy Cui, Ping Q DouAbstract:The investigation of novel anti-tumor agents that preferentially select for malignant cells with a tolerable toxicity level has been the focus of anti-cancer drug discovery. Our laboratories have previously reported that certain N-alkylthiolated beta-Lactams had DNA-damaging and apoptosis-inducing activity in various tumor lines but not in nontransformed cells. In the current study, we further delineated the effects of substitutions at C3 or N1 of the Lactam Ring for cell death-inducing capability with close attention paid to a discernible structure-activity relationship (SAR). We found that two beta-Lactam analogs (JG-5 and JG-19), both containing a branched-chain moiety at C3 of the Lactam Ring, exhibit potent apoptosis-inducing activity. Additionally, JG-5 exhibited superior in vitro biological activity over JG-19 owing to structural modifications made to substituents at the N1 and C3 positions of the Lactam Ring. Furthermore, the branched beta-Lactams were able to inhibit growth of mice beaRing breast cancer xenografts, associated with induction of DNA damage and apoptosis in tumor tissues. Our results strongly warrant further investigation into these novel beta-Lactams as potential anti-cancer therapeutics.
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Palladium-promoted derivatizations of novel C-fused penem Ring systems
Tetrahedron Letters, 1997Co-Authors: Monika I. Konaklieva, Edward TurosAbstract:Abstract Palladium-catalyzed coupling reactions and carboxylations are reported for the functionalization of bicyclic beta-Lactam Ring systems related to the penem family of antibiotics.
