690663-30-0

Upstream product

• 67-62-9 O-Methylhydroxylamin 
• 785-56-8 3,5-bis(trifluoromethyl)phenyl carboxylic acid chloride 
• 593-56-6 N-methoxylamine hydrochloride 

Downstream Products

• 690663-24-2 (Z)-O-methyl-3,5-bistrifluoromethylbenzohydroximoyl fluoride 
• 690663-25-3 (E)-O-methyl-3,5-bistrifluoromethylbenzohydroximoyl fluoride 
• 690663-23-1 (Z)-O-methyl-3,5-bistrifluoromethylbenzohydroximoyl bromide 

Relevant academic research and scientific papers

Mediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule

Molecules that are capable of disrupting cellular ion homeostasis offer unique opportunities to treat cancer. However, previously reported synthetic ion transporters showed limited value, as promiscuous ionic disruption caused toxicity to both healthy cells and cancer cells indiscriminately. Here we report a simple yet efficient synthetic K+ transporter that takes advantage of the endogenous subcellular pH gradient and membrane potential to site-selectively mediate K+/H+ transport on the mitochondrial and lysosomal membranes in living cells. Consequent mitochondrial and lysosomal damages enhanced cytotoxicity to chemo-resistant ovarian cancer stem cells (CSCs) via apoptosis induction and autophagy suppression with remarkable selectivity (up to 47-fold). The eradication of CSCs blunted tumor formation in mice. We believe this strategy can be exploited in the structural design and applications of next-generation synthetic cation transporters for the treatment of cancer and other diseases related to dysfunctional K+ channels.

Mechanism of Methoxide Ion Substitution in the Z and E Isomers of O-Methylbenzohydroximoyl Halides

Kinetics and stereochemical studies have been carried out on the reactions of the Z and E isomers of O-methylbenzohydroximoyl halides [1Z and 1E, ArC(X)= NOCH3] with sodium methoxide in 9:1 DMSO-methanol. The reactions of methoxide ion with hydroximoyl fluorides (X = F) are stereospecific. The reaction with 1Z (X = F) gives only the Z substitution product (1Z, X = OCH 3). The reaction of methoxide ion with 1E (X = F) is less selective, giving ca. 85% E substitution product. The Hammett ρ-values for the Z and E isomers (X = F) are +2.94 and +3.30, respectively. The element effects for 1Z (Ar = C6H5) are 2.21 (X = Br):1.00 (X = Cl):79.7 (X = F). The 1E element effects are (Ar = C6H5) 1.00 (X = Cl):8.3 (X = F) and (Ar = 4-CH3OC6H4) 1.97 (X = Br):1.00 (X = Cl):12.1 (X = F). The entropies of activation for these reactions are negative (for example, ΔS? = - 15 eu for 1Z and ΔS? = - 14 eu for 1E, Ar = 4-CH3OC6H 4, X = F). These experimental observations are consistent with a mechanism proceeding through a tetrahedral intermediate. Ab initio calculations were carried out to help explain the stereospecificity of these reactions. These calculations indicate that the tetrahedral intermediate from the Z isomer undergoes rapid elimination to the Z substitution product before stereomutation can take place. These calculations also show that the lowest barrier for rotation around the carbon-nitrogen single bond in the tetrahedral intermediate derived from 1E leads to an intermediate that eliminates fluoride ion to give E product.