Determination of the Carbonyl Group: Oximation and Other Methods

Schenk, George H.

doi:10.1016/b978-0-08-203484-1.50004-1

“…[36][37][38] Additionally, to increase the stability of the hydrazones, conjugated aldehydes were used. 39,40 These core aldehydes were prepared according to the previous syntheses (Scheme S1-4). [41][42][43][44] The contribution of the accessory motifs to MraY inhibition is substantial, as the core structures on their own bind and inhibit MraY nearly three orders of magnitude weaker than those of the original natural products.…”

Section: Design Of the Librarymentioning

confidence: 99%

Development of a Natural Product Optimization Strategy for inhibitors against the cell wall synthesis enzyme MraY, a promising antibacterial target

Yamamoto

¹

,

Sato

²

,

Hao

³

et al. 2023

Preprint

0

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Optimization of natural products is often required to improve their drug-like properties for therapeutic use. However, chemical modifications of natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to clinic. Here, we developed a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We applied this approach to a series of natural product inhibitors for MraY, an important target for the antibacterial development. Through construction and evaluation of the 686-compound library, we identified promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent new types of MraY inhibitors with unique pharmacological profiles.

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“…[36][37][38] Additionally, to increase the stability of the hydrazones, conjugated aldehydes were used. 39,40 These core aldehydes were prepared according to the previous syntheses (Scheme S1-4). [41][42][43][44] The contribution of the accessory motifs to MraY inhibition is substantial, as the core structures on their own bind and inhibit MraY nearly three orders of magnitude weaker than those of the original natural products.…”

Section: Design Of the Librarymentioning

confidence: 99%

Development of a Natural Product Optimization Strategy for inhibitors against the cell wall synthesis enzyme MraY, a promising antibacterial target

Yamamoto

¹

,

Sato

²

,

Hao

³

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Optimization of natural products is often required to improve their drug-like properties for therapeutic use. However, chemical modifications of natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to clinic. Here, we developed a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We applied this approach to a series of natural product inhibitors for MraY, an important target for the antibacterial development. Through construction and evaluation of the 686-compound library, we identified promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent new types of MraY inhibitors with unique pharmacological profiles.

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Liquid–liquid synthesis of oximes from carbonyl compounds: formation under neutral conditions and degradation at acidic hydrometallurgical process conditions

Kabugo

¹

,

Virolainen

²

,

Paatero

³

et al. 2016

J of Chemical Tech & Biotech

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BACKGROUND In order to elucidate kinetics in the synthesis of oxime liquid–liquid extraction reagents, used as ligands in hydrometallurgical copper production, the oximation reactions of salicylaldehyde and 2′‐hydroxyacetophenone with hydroxylamine were studied in a two‐phase system. Two experimental methods were applied: CSTR reactor under vigorous mixing and batch reactor under normal agitation. The reverse reaction in acidic conditions was also examined, because it results in hydroxyoxime reagent losses in copper liquid–liquid extraction process. RESULTS The overall oximation reaction was of a second‐order, first‐order with respect to each reactant. The estimated activation energy for oximation of salicylaldehyde was 34.2 kJ mol−1, and interfacial reaction rate constant at 40°C 4.81 × 10−3 L mol−1 s−1. The model used, including the empirical description for interfacial reactant concentrations, described the salicylaldehyde oximation reaction well over a wide concentration range. In the batch reactor more than 0.99 conversion for salicylaldehyde was achieved in 15 min at 50°C, but for 2′‐hydroxyacetophenone the maximum reaction conversion was only 0.17 at 70°C in 60 min. Both, aldoxime and ketoxime, were hydrolyzed into their corresponding carbonyl compounds in the presence of 180 g L−1 sulfuric acid. The ketoxime was completely converted into a ketone, but with the aldoxime 80% reagent degradation was observed at equilibrium. CONCLUSION A liquid–liquid system in neutral conditions is applicable for the oximation of aldehydes generated by degradation of hydroxyoxime solvent extraction reagents. For ketones the reaction is much slower. The degradation reaction was shown to be significant in conditions similar to the copper liquid–liquid extraction stripping stage. © 2016 Society of Chemical Industry

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Determination of the Carbonyl Group: Oximation and Other Methods

Cited by 3 publications

References 18 publications

Development of a Natural Product Optimization Strategy for inhibitors against the cell wall synthesis enzyme MraY, a promising antibacterial target

Development of a Natural Product Optimization Strategy for inhibitors against the cell wall synthesis enzyme MraY, a promising antibacterial target

Development of a Natural Product Optimization Strategy for inhibitors against the cell wall synthesis enzyme MraY, a promising antibacterial target

Liquid–liquid synthesis of oximes from carbonyl compounds: formation under neutral conditions and degradation at acidic hydrometallurgical process conditions

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