1004524-53-1Relevant articles and documents
Broad spectrum antibiotic arylomycin analogs
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Page/Page column 107; 108, (2015/12/30)
Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectrum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.
Intramolecular suzuki-miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A2and B2
Dufour, Jeremy,Neuville, Luc,Zhu, Jieping
supporting information; experimental part, p. 10523 - 10534 (2010/11/04)
Development of the total syntheses of arylomycins A1 and B 2 is detailed. Key features of our approach include 1) formation of 14-membered meta, meta-cyclophane by an intramolecular Suzuki-Miyaura reaction; 2) incorporation of N-Me-4-hydroxyphenylglycine into the cyclization precursor, which avoids the late-stage low-yielding N-methylation step; 3) segment coupling of a fully elaborated peptide side chain to the macrocycle, which makes the synthesis highly convergent. Overall, arylomycin A2 was obtained in 13 steps from L-Tyr for the longest linear sequence, in 13% overall yield. Arylomycin B2 was synthesized in 10 steps from L-3-nitro-Tyr, in 10% overall yield.
Structural and initial biological analysis of synthetic arylomycin A 2
Roberts, Tucker C.,Smith, Peter A.,Cirz, Ryan T.,Romesberg, Floyd E.
, p. 15830 - 15838 (2008/09/19)
The growing threat of untreatable bacterial infections has refocused efforts to identify new antibiotics, especially those acting by novel mechanisms. While the inhibition of pathogen proteases has proven to be a successful strategy for drug development,
