34595-06-7

Upstream product

• 6630-33-7 ortho-bromobenzaldehyde 
• 122-52-1 triethyl phosphite 
• 13294-40-1 ortho-nitro-phenylphosphonate diethylique 
• 31238-50-3 (2-aminophenyl)phosphonic acid diethyl ester 
• 34595-07-8 2-Cyanphenylphosphonsaeurediethylester 
• 89-98-5 2-chloro-benzaldehyde 
• 762-04-9 phosphonic acid diethyl ester 

Relevant academic research and scientific papers

Synthesis of ortho-formylphenylphosphonic acids as covalent probes of active site lysines

During the course of an investigation of targeted inhibition of DNA polymerase beta (pol β) lyase activity using small molecules, we observed the formation of an aldimine between (2-formyl)phenylphosphonic acid (2FPP) and butylamine under basic aqueous conditions; complete deprotonation of the phosphonate group was required to stabilize the imine product. Results of computational docking studies suggested that the reaction of Lys-72 on the lyase active site with an aldehyde group could be facilitated by a proximal phosphonate, not only because of the phosphonate’s ability to mimic phosphate interacting with the DNA binding site, but also because of its ability to shield the imine against hydrolysis. Novel pol β lyase inhibitors were thus prepared using a 2FPP analogue with an amine linker; P-C bond formation in synthesis of this intermediate was possible with an unprotected aldehyde using palladium-catalyzed, microwave-assisted Michaelis–Arbuzov chemistry. These compounds, and structurally related derivatives lacking the aldehyde or phosphonate, were evaluated in an assay for pol β to assess their potential for inhibition.

Phosphonofluoresceins: Synthesis, Spectroscopy, and Applications

Xanthene fluorophores, like fluorescein, have been versatile molecules across diverse fields of chemistry and life sciences. Despite the ubiquity of 3-carboxy and 3-sulfonofluorescein for the last 150 years, to date, no reports of 3-phosphonofluorescein exist. Here, we report the synthesis, spectroscopic characterization, and applications of 3-phosphonofluoresceins. The absorption and emission of 3-phosphonofluoresceins remain relatively unaltered from the parent 3-carboxyfluorescein. 3-Phosphonofluoresceins show enhanced water solubility compared to 3-carboxyfluorescein and persist in an open, visible light-absorbing state even at low pH and in low dielectric media while 3-carboxyfluoresceins tend to lactonize. In contrast, the spirocyclization tendency of 3-phosphonofluoresceins can be modulated by esterification of the phosphonic acid. The bis-acetoxymethyl ester of 3-phosphonofluorescein readily enters living cells, showing excellent accumulation (>6x) and retention (>11x), resulting in a nearly 70-fold improvement in cellular brightness compared to 3-carboxyfluorescein. In a complementary fashion, the free acid form of 3-phosphonofluorescein does not cross cellular membranes, making it ideally suited for incorporation into a voltage-sensing scaffold. We develop a new synthetic route to functionalized 3-phosphonofluoresceins to enable the synthesis of phosphono-voltage sensitive fluorophores, or phosVF2.1.Cl. Phosphono-VF2.1.Cl shows excellent membrane localization, cellular brightness, and voltage sensitivity (26% ΔF/F per 100 mV), rivaling that of sulfono-based VF dyes. In summary, we develop the first synthesis of 3-phosphonofluoresceins, characterize the spectroscopic properties of this new class of xanthene dyes, and utilize these insights to show the utility of 3-phosphonofluoresceins in intracellular imaging and membrane potential sensing.

An improved procedure for the synthesis of aryl phosphonates by palladium-catalysed cross-coupling of aryl halides and diethyl phosphite in polyethylene glycol

A general and greener protocol for the synthesis of aryl phosphonates by the cross-coupling of aryl halides and diethyl phosphite using tetrakis(triphenylphosphine)palladiume/triethylamine/polyethylene glycol 600 [Pd(PPh3)4/ Et3N/PEG 600] as an efficient catalytic system has been developed. This procedure also avoids hazardous solvents and is therefore an eco-friendly alternative to the existing methods.