- A detailed study of antibacterial 3-acyltetramic acids and 3-acylpiperidine-2,4-diones
-
Inspired by the core fragment of antibacterial natural products such as streptolydigin, 3-acyltetramic acids and 3-acylpiperidine-2,4-diones have been synthesised from the core heterocycle by direct acylation with the substituted carboxylic acids using a strategy which permits ready access to a structurally diverse compound library. The antibacterial activity of these systems has been established against a panel of Gram-positive and Gram-negative bacteria, with activity mostly against the former, which in some cases is very potent. Data consistent with modes of action against undecaprenylpyrophosphate synthase (UPPS) and/or RNA polymerase (RNAP) for a small subset of the library has been obtained. The most active compounds have been shown to exhibit binding at known binding sites of streptolydigin and myxopyronin at UPPS and RNAP. These systems offer potential for their antibacterial activity, and further demonstrate the use of natural products as biologically validated starting points for drug discovery.
- Jeong, Yong-Chul,Bikadi, Zsolt,Hazai, Eszter,Moloney, Mark G.
-
supporting information
p. 1826 - 1837
(2014/08/18)
-
- Agonists for Antimicrobial Peptide Systems
-
Short chain fatty acids (SCFAs) and glycerol esters of SCFAs not previously used for that purpose are provided for use as a medicament for treating, preventing or counteracting microbial infections in animals, including humans, by stimulating the innate antimicrobial peptide defense system. Preferred compounds include phenyl substituted short chain fatty acids (SCFAs) derivatives and. Also provided are methods and compositions for treating, preventing or counteracting microbial infections, including bacterial, viral, fungal, and parasitic infections, by administration of medicaments comprising a secretagogue-effective amount of the compounds of the invention.
- -
-
-
- Ruthenium Tetroxide Oxidation of N-Acylated Alkylamines: A New General Synthesis of Imides
-
Oxidation of various N-acylalkylamines with ruthenium tetroxide (RuO4) was systematically investigated.N-acylalkylamines having an electron-donating group at the α- or β-position with respect to amide nitrogen or an electron-donating alkyl function in the acyl group were smoothly oxidized to the corresponding imides in excellent yields.On the other hand, N-acylalkylamines having an electron-withdrawing group were not oxidized at all, and most of the starting material was recovered.It appears that the reactivity of N-acylalkylamines is closely correlated with the acidity of the carboxylic acid from which the N-acyl group is derived, and also with the electron density at the methylene moiety adjacent to the amide nitrogen atom.Keywords---oxidation; ruthenium tetroxide oxidation; imide synthesis; acyclic imide; amide; ruthenium tetroxide; substituent effect
- Tanaka, Ken-Ichi,Yoshifuji, Shigeyuki,Nitta, Yoshihiro
-
p. 364 - 369
(2007/10/02)
-