85908-57-2

Upstream product

• 1623-14-9 ethyl phosphate 
• 108-95-2 phenol 
• 33444-24-5 O_.O-Diaethyl-O-phenylselenophosphat 
• 3426-89-9 phenyl phosphorodichloridite 
• 1498-51-7 ethyl phosphodichloridite 
• 55811-88-6 C₁₀H₁₅ClO₃PSe⁽¹⁺⁾*Cl^(1-) 
• 7022-99-3 Phosphorigsaeure-ethyl-phenylester 
• 770-12-7 O-phenyl phosphorodichloridate 
• 64-17-5 ethanol 

Downstream Products

• 1169705-81-0 O-ethyl O-phenyl O-2-(stearamido)ethyl phosphate 
• 5449-04-7 N-phenyl O-ethyl O-phenyl phosphoramidate 
• 72163-96-3 amidophosphoric acid ethyl ester-phenyl ester 
• 46207-73-2 ethyl phenyl hydrogen phosphate 

Relevant academic research and scientific papers

Phosphate linkers with traceable cyclic intermediates for self-immolation detection and monitoring

Self-immolation (SI) is the key principle of ProTide nucleotide prodrugs such as remdesivir, which is currently used to treat COVID-19 patients. Developing novel tailor-made SI systems requires new analytical methods for the detection and monitoring of SI. We developed a robust method for SI analysis using novel phosphate-based SI linkers with NMR traceable cyclic intermediates to distinguish SI from alternative fragmentation pathways and to monitor cargo release in real time.

Phosphate-Based Self-Immolative Linkers for Tuneable Double Cargo Release

Phosphorus-based self-immolative (SI) linkers offer a wide range of applications, such as smart materials and drug-delivery systems. Phosphorus SI linkers are ideal candidates for double-cargo delivery platforms because they have a higher valency than carbon. A series of substituted phosphate linkers was designed for releasing two phenolic cargos through SI followed by chemical hydrolysis. Suitable modifications of the lactate spacer increased the cargo release rate significantly, from 1 day to 2 hours or 5 minutes, as shown for linkers containing p-fluoro phenol. In turn, double cargo linkers bearing p-methyl phenol released their cargo more slowly (4 days, 4 hours, and 15 minutes) than their p-fluoro analogues. The α-hydroxyisobutyrate linker released both cargos in 25 minutes. Our study expands the current portfolio of SI constructs by providing a double cargo delivery option, which is crucial to develop universal SI platforms.

Sterically-Controlled Self-Immolation in Phosphoramidate Linkers Triggered by Light

Phosphoramidate prodrugs stand out for their applications as drug delivery systems. However, information on their activation remains limited to prodrug half-live and metabolite structure, which hinders their development. Considering the lack of data on ph

Reactive cyclic intermediates in the ProTide prodrugs activation: Trapping the elusive pentavalent phosphorane

Nucleotide prodrugs (ProTides) based on phosphate or phosphonate compounds are potent and successfully marketed antiviral drugs. Although their biological properties are well explored, experimental evidence on the mechanism of their activation pathway is still missing. In this study, we synthesized two ProTide analogues, which can be activated by UV light. Using 31P and 13C NMR spectroscopy with in situ irradiation, we followed the ProTide activation pathway in various solvents, and we detected the first proposed intermediate and the monoamidate product. Furthermore, we used mass spectrometry (MS) coupled with infrared spectroscopy in the gas phase to detect and to characterize the elusive cyclic pentavalent phosphorane and cyclic acyl phosphoramidate intermediates. Our combined NMR and MS data provided the first experimental evidence of the cyclic intermediates in the activation pathway of ProTide prodrugs.

Kinetics and mechanism of the anilinolysis of aryl ethyl isothiocyanophosphates in acetonitrile

The nucleophilic substitution reactions of Y-aryl ethyl isothiocyanophosphates with substituted X-anilines and deuterated X-anilines were investigated kinetically in acetonitrile at 75.0 oC. The free energy relationships with X in the nucleophiles exhibited biphasic concave downwards with a break point at X = H. A stepwise mechanism with rate-limiting bond formation for strongly basic anilines and with rate-limiting bond breaking for weakly basic anilines is proposed based on the negative and positive ?XY values, respectively. The deuterium kinetic isotope effects (DKIEs; kH/kD) changed gradually from primary normal with strongly basic anilines, via primary normal and secondary inverse with aniline, to secondary inverse with weakly basic anilines. The primary normal and secondary inverse DKIEs were rationalized by frontside attack involving hydrogen bonded, four-center-type TSf and backside attack involving in-line-type TSb, respectively.

Synthesis and evaluation of phosphoramidate and phosphorothioamidate analogues of amiprophos methyl as potential antimalarial agents

A series of phosphoramidate and phosphorothioamidate compounds based on the lead antitubulin herbicidal agents amiprophos methyl (APM) and butamifos were synthesised and evaluated for antimalarial activity. Of these compounds, phosphorothioamidates were m

Insecticidal activity of some new amidophosphoric acid esters containing substituted pyridine moieties

Some new amidophosphoric acid esters containing substituted pyridine moieties were synthesized by the reaction of O-aryl, O-ethyl phosphoryl chlorides with 3-(aminomethyl)pyridine and 5-(aminomethyl)-2-chloropyridine. Characterization was done by 1H NMR,

Kinetics and mechanism of the aminolysis of aryl ethyl chloro and chlorothio phosphates with anilines

The reactions of ethyl Y-phenyl chloro (1) and chlorothio (2) phosphates with X-anilines in acetonitrile at 55.0 °C are studied kinetically and theoretically. Kinetic results yield the primary kinetic isotope effects (k H/kD = 1.07-1.80 and 1.06-1.27 for 1 and 2, respectively) with deuterated aniline (XC6H4ND2) nucleophiles, and the cross-interaction constants ρXY = -0.60 and -0.28 for 1 and 2, respectively. A concerted mechanism involving a partial frontside attack through a hydrogen-bonded, four-center-type transition state is proposed. The large ρX (ρnuc = -3.1 to -3.4) and βX (βnuc = 1.1-1.2) values seem to be characteristic of the anilinolysis of phosphates and thiophosphates with the Cl leaving group. Because of the relatively large size of the aniline nucleophile, the degree of steric hindrance could be the decisive factor that determines the direction of the nucleophilic attack to the phosphate and thiophosphate substrates with the relatively small-sized Cl leaving group. This journal is The Royal Society of Chemistry.

Synthesis and quantitative structure-activity relationships of phosphoramidates and phosphorodiamidates incorporating amino acid esters

Two series of O-aryl and N-aryl O-ethyl phosphoramidates and phosphorodiamidates respectively containing α-amino acid ester moieties have been synthesized and characterized by 1H NMR, IR and mass spectroscopy. Stepwise multiple regression analy

Quantitative structure-activity relationship of a series of N-aryl O- aryl phosphoramidate insecticides

A series of O-ethyl O-aryl N-aryl phosphoramidates was prepared and examined for housefly contact toxicity and acetylcholinesterase (ACHE) inhibition. Results showed a moderate toxicity and enzyme inhibition effect. These biological properties correlated