- Combinatorial synthesis and in vitro evaluation of a biaryl hydroxyketone library as antivirulence agents against mrsa
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Antibiotic resistance coupled with decreased development of new antibiotics necessitates the search for novel antibacterial agents. Antivirulence agents offer an alternative to conventional antibiotics. In this work, we report on a family of small-molecule antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA), the most widespread bacterial pathogen. Structure-activity relationship studies led to the development of a concise synthesis of a 148-member biarylhydroxyketone library. An acylation bond-forming process afforded resorcinols (1) and aryloxy acetonitriles (2) as synthons. A Lewis-acid-activated Friedel-Crafts' acylation step involving a nitrile functionality of 2 by ZnCl2, followed by nucleophilic attack by 1 was executed to obtain biaryl hydroxyketones in excellent yields. A large number of products crystallized. This strategy affords a range of biarylhydroxyketones in a single step. This is the first collective synthetic study documenting access to this class of compounds through a single synthetic operation. In vitro efficacy of compounds in this library was evaluated by a rabbit erythrocyte hemolysis assay. The most efficacious compound, 4f-12, inhibits hemolysis by 98.1 ± 0.1% compared to control in the absence of the compound.
- Yu, Guanping,Kuo, David,Shoham, Menachem,Viswanathan, Rajesh
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supporting information
p. 85 - 91
(2014/03/21)
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- A new synthesis of 2-aryloxypropionic acids derivatives via selective mono-C-methylation of methyl aryloxyacetates and aryloxyacetonitriles with dimethyl carbonate
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A one-pot procedure for the mono-C-methylation of methyl aryloxyacetates and aryloxyaceto nitriles by dimethyl carbonate (DMC) is reported. The reaction is carried out in an autoclave at high temperatures (180-200°C) and in the presence of a base (K2
- Bomben, Andrea,Marques, Carlos A.,Selva, Maurizio,Tundo, Pietro
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p. 11573 - 11580
(2007/10/02)
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