76063-11-1

Upstream product

• 2127-03-9 2,2'-dipyridyldisulphide 
• 1821-12-1 4-Phenylbutyric acid 
• 2637-34-5 2-Sulfanylpyridine 
• 18496-54-3 phenylbutyric acid chloride 

Downstream Products

• 28123-49-1 1,8-Diphenyl-octane-4,5-dione 
• 76063-14-4 (+/-)-5-hydroxy-1,8-diphenyloctan-4-one 
• 625445-62-7 1-cyclopentyl-4-phenylbutan-1-one 
• 78427-96-0 1-phenyloctan-4-one 

Relevant academic research and scientific papers

An Aromatic Hydroxyamide Attenuates Multiresistant Staphylococcus aureus Toxin Expression

Methicillin-resistant Staphylococcus aureus (MRSA) causes severe infections with only few effective antibiotic therapies currently available. To approach this challenge, chemical entities with a novel and resistance-free mode of action are desperately needed. Here, we introduce a new hydroxyamide compound that effectively reduces the expression of devastating toxins in various S. aureus and MRSA strains. The molecular mechanism was investigated by transcriptome analysis as well as by affinity-based protein profiling. Down-regulation of several pathogenesis associated genes suggested the inhibition of a central virulence-related pathway. Mass spectrometry-based chemical proteomics revealed putative molecular targets. Systemic treatment with the hydroxyamide showed significant reduction of abscess sizes in a MRSA mouse skin infection model. The absence of resistance development in vitro further underlines the finding that targeting virulence could lead to prolonged therapeutic options in comparison to antibiotics that directly address bacterial survival. Disarming MRSA: A new hydroxyamide compound effectively reduces the expression of devastating toxins in various S. aureus and MRSA strains. The molecular mechanism was investigated by transcriptome analysis, as well as by affinity-based protein profiling. Systemic treatment with the hydroxyamide showed significant reduction of abscess sizes in an MRSA mouse skin infection model.

A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.

Light-Driven Vitamin B12-Catalysed Generation of Acyl Radicals from 2-S-Pyridyl Thioesters

Acyl radicals are invaluable intermediates in organic synthesis, however their generation remains challenging. Herein, we present an unprecedented light-driven, cobalt-catalysed method for the generation of acyl radicals from readily available 2-S-pyridyl thioesters. The synthetic potential of this methodology was demonstrated in the Giese-type acylation of activated olefins in the presence of heptamethyl cobyrrinate. This vitamin B12 derivative proved to be the most efficient catalyst in the studied process. The developed method features broad substrate scope (38 examples), good functional group tolerance, and mild reaction conditions. Moreover, it is easily scalable (illustrated on a 20-fold scale-up procedure), enabling its preparative use. Mechanistic studies revealed that the reaction proceeds via a radical pathway with the key steps involving the formation of an acyl-vitamin B12 complex and subsequent photolysis of the Co?C bond. (Figure presented.).

INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME

Compounds of formula (I) are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus.