1837-93-0Relevant articles and documents
Hydrogen peroxide based oxidation of hydrazines using HBr catalyst
Du, Wanting,Ma, Zichao,Shao, Liming,Wang, Jian
, (2021/11/18)
Azo compounds (RN = NR′) are an important class of organic molecules that find wide application in organic synthesis. Herein, we report an efficient, practical and metal-free oxidation of hydrazines (RNH-NHR’) to azo compounds using 5 mol% HBr and hydrogen peroxide as terminal oxidant. This new method has been demonstrated by 40 examples with excellent yields. In addition, we showcased two examples of the one-pot sequential reactions involving our hydrazine oxidation/hydrolysis/Heck reaction or Cu-catalyzed N-arylation with aryl boronic acid. The distinct advantages of this protocol include metal-free catalysis, waste prevention, and easy operation.
Photosensitive and Photoswitchable TRPA1 Agonists Optically Control Pain through Channel Desensitization
Luo, Jiajie,Qi, Hang,Qiao, Zhen,Tang, Xiaowen,Tang, Yi-Quan,Wang, KeWei,Wei, Ningning,Yin, Zhengji,Zhang, Yanru,Zhou, Qiqi,Zhu, Wei
supporting information, p. 16282 - 16292 (2021/11/12)
Transient receptor potential ankyrin 1 (TRPA1) channel, as a nonselective ligand-gated cation channel robustly in dorsal root ganglion sensory neurons, is implicated in sensing noxious stimuli and nociceptive signaling. However, small-molecule tools targeting TRPA1 lack temporal and spatial resolution, limiting their use for validation of TRPA1 as a therapeutic target for pain. In our previous work, we found that 4,4′-(diazene-1,2-diyl)dianiline (AB1) is a photoswitchable TRPA1 agonist, but the poor water solubility and activity hinder its further development. Here, we report a series of specific and potent azobenzene-derived photoswitchable TRPA1 agonists (series 1 and 2) that enable optical control of the TRPA1 channel. Two representative compounds 1g and 2c can alleviate capsaicin-induced pain in the cheek model of mice through channel desensitization but not in TRPA1 knockout mice. Taken together, our findings demonstrate that photoswitchable TRPA1 agonists can be used as pharmacological tools for study of pain signaling.
Structure requirements for anaerobe processing of azo compounds: Implications for prodrug design
Gavin, Jason,Ruiz, Juan F. Marquez,Kedziora, Kinga,Windle, Henry,Kelleher, Dermot P.,Gilmer, John F.
, p. 7647 - 7652 (2013/02/21)
This Letter generalizes the metabolism of the azo class of compounds by Clostridium perfringens, an anaerobe found in the human colon. A recently reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release the drug when incubated with the bacteria, while the para-aminobenzoic acid (PABA) based analogue did not. Instead, it showed a new HPLC peak with a relatively close retention time to the parent which was identified by LCMS as the partially reduced hydrazine product. This Letter investigates azoreduction across a panel of substrates with varying degrees of electronic and steric similarity to the PABA-based compound. Azo compounds with an electron donating group on the azo-containing aromatic ring showed immediate disproportionation to their parent amines without any detection of hydrazine intermediates by HPLC. Compounds containing only electron withdrawing groups are partially and reversibly reduced to produce a stable detectable hydrazine. They do not disproportionate to their parent amines, but regenerate the parent azo compound. This incomplete reduction is relevant to the design of azo-based prodrugs and the toxicology of azo-based dyes.
