544-47-8Relevant articles and documents
Synthesis of difluoromethyl and deuterium-labeled difluoromethyl thioethers from aliphatic electrophiles
Ding, Tianqi,Jiang, Lvqi,Yi, Wenbin
, p. 3995 - 3998 (2020/04/17)
A one-pot difluoromethylthiolation of alkyl electrophiles with thiourea and diethyl bromodifluoromethylphosphonate is described. The transition-metal-free approach, readily available reagents, and mild conditions provide a practical way for the synthesis of difluoromethyl thioethers. By changing the "H" source to the most commonly used "D" sources CD3OD and D2O, this strategy enables efficient synthesis of SCF2D-substituted molecules in good yields with high levels of D incorporation.
Pathway-directed screen for inhibitors of the bacterial cell elongation machinery
Buss, Jackson A.,Baidin, Vadim,Welsh, Michael A.,Flores-Kim, Josué,Cho, Hongbaek,McKay Wood,Uehara, Tsuyoshi,Walker, Suzanne,Kahne, Daniel,Bernhardta, Thomas G.
, (2019/01/04)
New antibiotics are needed to combat the growing problem of resistant bacterial infections. An attractive avenue toward the discovery of such next-generation therapies is to identify novel inhibitors of clinically validated targets, like cell wall biogenesis. We have therefore developed a pathway-directed whole-cell screen for small molecules that block the activity of the Rod system of Escherichia coli. This conserved multiprotein complex is required for cell elongation and the morphogenesis of rod-shaped bacteria. It is composed of cell wall synthases and membrane proteins of unknown function that are organized by filaments of the actin-like MreB protein. Our screen takes advantage of the conditional essentiality of the Rod system and the ability of the beta-lactam mecillinam (also known as amdinocillin) to cause a toxic malfunctioning of the machinery. Rod system inhibitors can therefore be identified as molecules that promote growth in the presence of mecillinam under conditions permissive for the growth of Rod– cells. A screen of 690,000 compounds identified 1,300 compounds that were active against E. coli. Pathway-directed screening of a majority of this subset of compounds for Rod inhibitors successfully identified eight analogs of the MreB antagonist A22. Further characterization of the A22 analogs identified showed that their antibiotic activity under conditions where the Rod system is essential was strongly correlated with their ability to suppress mecillinam toxicity. This result combined with those from additional biological studies reinforce the notion that A22-like molecules are relatively specific for MreB and suggest that the lipoprotein transport factor LolA is unlikely to be a physiologically relevant target as previously proposed.
Tert -Butyl Hypochlorite Mediated Oxidative Chlorination of S -Alkylisothiourea Salts: Synthesis of Sulfonyl Chlorides
Qiu, Kui,Wang, Rennan
, p. 3186 - 3190 (2015/10/19)
Under neutral conditions, a variety of S-alkylisothiourea salts were smoothly converted into the corresponding sulfonyl chlorides through tert-butyl chlorite mediated oxidative chlorination in good to excellent yields after simple purification. In addition to the environmental and procedural advantages of this method, the neutral conditions potentially make it applicable to substrates that bear acid-sensitive functional groups. For example, the Cbz-protected 2-aminoethanesulfonyl chloride could be synthesized in moderate to good yields under the current neutral conditions, and the acid-sensitive Cbz-protecting group was not affected.
