123811-74-5Relevant articles and documents
Cystobactamid 507: Concise Synthesis, Mode of Action, and Optimization toward More Potent Antibiotics
Elgaher, Walid A. M.,Hamed, Mostafa M.,Baumann, Sascha,Herrmann, Jennifer,Siebenbürger, Lorenz,Krull, Jana,Cirnski, Katarina,Kirschning, Andreas,Br?nstrup, Mark,Müller, Rolf,Hartmann, Rolf W.
, p. 7219 - 7225 (2020/05/08)
Lack of new antibiotics and increasing antimicrobial resistance are among the main concerns of healthcare communities nowadays, and these concerns necessitate the search for novel antibacterial agents. Recently, we discovered the cystobactamids—a novel natural class of antibiotics with broad-spectrum antibacterial activity. In this work, we describe 1) a concise total synthesis of cystobactamid 507, 2) the identification of the bioactive conformation using noncovalently bonded rigid analogues, and 3) the first structure–activity relationship (SAR) study for cystobactamid 507 leading to new analogues with high metabolic stability, superior topoisomerase IIA inhibition, antibacterial activity and, importantly, stability toward the resistant factor AlbD. Deeper insight into the mode of action revealed that the cystobactamids employ DNA minor-groove binding as part of the drug–target interaction without showing significant intercalation. By designing a new analogue of cystobactamid 919-2, we finally demonstrated that these findings could be further exploited to obtain more potent hexapeptides against Gram-negative bacteria.
Aluminum-catalyzed asymmetric alkylations of pyridyl-substituted alkynyl ketones with dialkylzinc reagents
Friel, Donna K.,Snapper, Marc L.,Hoveyda, Amir H.
supporting information; experimental part, p. 9942 - 9951 (2009/02/04)
Alkylations of pyridyl-substituted ynones with Et2Zn and Me 2Zn, promoted by amino acid-based chiral ligands in the presence of Al-based alkoxides, afford tertiary propargyl alcohols efficiently in 57% to >98% ee. Two easily accessib
An Improved Synthesis of Homoproline and Derivatives
Shuman, Robert T.,Ornstein, Paul L.,Paschal, Jonathan W.,Gesellchen, Paul D.
, p. 738 - 741 (2007/10/02)
An improved, general synthesis of substituted homoprolines has been developed by using readily available substituted pyridines (1).A key step in this synthetic procedure involves the known conversion of pyridine-N-oxides to 2-cyanopyridines (3) in nearly quantitative yields.The resulting nitriles are hydrolyzed to the corresponding pyridine-2-carboxylic acids (4).Subsequent reduction of the aromatic ring with PtO2/H2 gives the homoprolines (5) in good yields as racemic cis isomers.This procedure also can be utilized for the preparation of 5,6-benzohomoprolines fromthe appropriate quinoline precursors.The N-tert-butyloxycarbonyl (Boc) derivatives of these amino acids (useful intermediates for peptide synthesis) were also prepared in good yields.
