Novel N-chloroheterocyclic antimicrobials

Francavilla, Charles; Turtle, Eric D; Kim, Bum; O'Mahony, Donogh J. R.; Shiau, Timothy P; Low, Eddy; Alvarez, Nichole; Celeri, Chris; D'Lima, Louisa; Friedman, Lisa; Ruado, Francis; Xu, Ping; Zuck, Meghan; Anderson, Mark; Najafi, Ramin; Jain, Rakesh

doi:10.1016/j.bmcl.2011.03.035

Cited by 11 publications

(2 citation statements)

References 23 publications

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“…Usually, 1,3,5- and 1,3,5,5-substituted hydantoins are obtained from the substitution by alkylation, acylation, or Mitsunobu reaction of N- 1 and/or N- 3 positions of hydantoins. ,,,− The hydantoin core could be prepared from the Bucherer–Bergs reaction and then undergo a double substitution. ,− Analogues of phenytoin were notably prepared with this procedure. ,− Acylation methods gave N- acylated- N- chloro-hydantoins that were then used as chlorine source and a polymer-linked chiral hydantoin used as an auxiliary in asymmetric aldol reactions . Chlorohydantoins were besides obtained from the treatment of the nonsubstituted hydantoins with trichloroisocyanuric acid (TCCA) , or hypochlorites. − The preparation of the textile antimicrobial additive 1-chloro-3-ethyl-5,5-dimethylhydantoin (CEDMH) with calcium hypochlorite by mechanochemistry was recently reported by Konnert et al, providing a clean procedure with high yields and easy workup …”

Section: 35- and 1355-substituted Hydantoinsmentioning

confidence: 99%

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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The review highlights the hydantoin syntheses presented from the point of view of the preparation methods. Novel synthetic routes to various hydantoin structures, the advances brought to the classical methods in the aim of producing more sustainable and environmentally friendly procedures for the preparation of these biomolecules, and a critical comparison of the different synthetic approaches developed in the last twelve years are also described. The review is composed of 95 schemes, 8 figures and 528 references for the last 12 years and includes the description of the hydantoin-based marketed drugs and clinical candidates.

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Section: 35- and 1355-substituted Hydantoinsmentioning

confidence: 99%

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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“…The recent trend with environmental protection agencies worldwide has been to recommend usage of only certain class of compounds which have minimal toxicity to humans, animals, avian, and aquatic organisms [22,23]. These heterocyclic compounds have low toxicity profile [24][25][26][27] and yet the cost of these pesticides remains a concern [28]. This originates from the reason that the heterocyclic ring structures usually have low reaction yields [29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Efficient bulk scale synthesis of popular pesticide synthon: tetrachlorothiophene

Reddy

Chandrappa

Gowda³

et al. 2017

Catalysis, Structure & Reactivity

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Broad spectrum pesticides are molecules which act across a range of pests. The popular class of compounds with this property are thiacloprid, nitenpyram, ethaboxam, silthiofam, 3,3,4,4-tetrachloro tetrahydro thiophene etc. Interestingly, all these compounds possess at least one heterocyclic ring like thiophene, furan, and imidazole etc. in their structure. Among the synthons available for synthesis of neonicotinoids, tetrachlorothiophene is unique. The bulk scale synthesis of tetrachlorothiophene is reported only by cyclization of hexachloro-1,3-butadiene. The reaction yields of synthesis of this synthon are around 45%. We report silica-coated magnetic nanoparticles as a generic catalyst for this cyclization reaction yielding tetrachlorothiophene. The yield improvement is 50-60% more compared to original yield. The distillate crystallization in methanol yielded >98% pure compound compared to typical 90-92% in conventional process. The proposed reaction uses reusable silica-coated 40 nm size magnetic nanoparticles and the catalyst itself is of low cost and reaction conditions are mild.

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Unravelling the mechanism of intracellular oxidation of thiols by (N‐Cl)‐Taurine

Fernández

García

Armesto

et al. 2013

J of Physical Organic Chem

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Myeloperoxidase, a heme enzyme stored in high amounts in neutrophils and monocytes, produces reactive oxygen species that are involved in the innate mammalian response to infection; among these, the most reactive is HOCl, generated by oxidation of Cl À in the presence of H 2 O 2 . This powerful oxidant reacts very fast with protein side chains and peptide bonds. Taurine ( À O 3 SCH 2 CH 2 NH 3 + ), present in high concentrations in human neutrophils, traps the HOCl to yield (N-Cl)-Taurine, much less toxic and reactive; it is a long-lived oxidant which contributes to the killing of pathogenic organisms and plays a role in the inflammatory response. Kinetic data suggest that (N-Cl)-Tau reacts with cysteine and glutathione, two relevant thiols in mammals, via two pathways: direct oxidation (chlorination) of the thiolate by (N-Cl)-Tau involving general-acid catalysis, and, the major one, (N-Cl)-Tau hydrolysis followed by fast chlorine transfer from the so-formed HOCl/ClO À mixture to the corresponding thiolate, despite the highly unfavorable hydrolysis equilibrium (K H =10 À8 M). Scavenging of HOCl by strong nucleophiles like thiolates opens an effective reactive channel. Theoretical calculations, at the B3LYP/6-311++G(d,p) level of theory and using the SMD model to simulate aqueous salvation, agree with the experimental behavior, predicting that both the chlorine and the proton are almost half transferred at the transition state in the direct, general-acid catalyzed, chlorination of the thiolate by (N-Cl)-Tau. Under physiological conditions, the hydrolysis of (N-Cl)-Tau is the main responsible of the oxidation of intracellular thiols far away from the site of HOCl enzymatic production.

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Novel N-chloroheterocyclic antimicrobials

Cited by 11 publications

References 23 publications

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Efficient bulk scale synthesis of popular pesticide synthon: tetrachlorothiophene

Unravelling the mechanism of intracellular oxidation of thiols by (N‐Cl)‐Taurine

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