Phosphoramidous fluorides

Phosphoramidous fluorides, 13 383-389 Phosphoranes, 16 47 cage compounds, 30 246 as propellanes, 33 268 Phosphorescence, 19 68 Phosphoric acid ester amides, reaction with hexafluoroacetone, 30 237 Phosphoric acids, condensed, properties of, 5 220... 

Condensation of sodium phenoxide witli 2,2,2-trifluoroethyl iodide gives a product of direct substitution in a low yield, several other ethers are formed by eliminatton-addition reactions [7] Use of mesylate as a leaving group and hex amethyl phosphoramide (HMPA) as a solvent increases the yield of the substitution [S] Even chlorine can be replaced when the condensation is performed with potassium fluoride and acetic acid at a high temperature [9] (equations 6-8)... 

Acid fluorides can be used for a elean preparation of amides.9 96 The use of silylated amines is an elegant alternative, sinee liberated fluoride progressively desilylates them to more nucleophilic species. The reaction has to be started with a catalytic amount of fluoride (TBAF).92 Stannyl amines97 or phosphoryl amines (phosphoramides)98 have been used in similar reactions. 

The synthesis of a nucleotide-like phosphoramidite building block in which the nucleic base has been replaced by a tert-butyldimethylsilyl-protected styrene glycol (47) has been described. After its incorporation in an oligonucleotide by automated synthesis, the terminal alcohol has been oxidized with NaI04 after fluoride deprotection. A similar phosphoramidate in which the nucleic base has been replaced by an alkyl diol (48) has been incorporated in an oligonucleotide and further conjugated with biotin after oxidation to the aldehydic functional-ity. ... 

T5q>e A NTE inhibitors produce OPIDN and include certain phosphates, phosphonates, and phosphoramidates. V tiien t)q)e A compounds inactivate NTE, it rapidly becomes intractable to reactivation by powerful nucleophiles, such as oximes or fluoride. This inability to be reactivated has been interpreted as evidence of aging. Because loss of reactivatability takes place within minutes of inhibition by t5q>e A inhibitors and OPIDN takes 1-A weeks to develop, aging of NTE is not the rate-limiting step in the disease process (Johnson, 1982). 

Milatovic, D., Johnson, M.K., 1993. Reactivation of phosphoramidated acetylcholinesterase and neuropathy target esterase by treatment of inhibited enzyme with potassium fluoride. Chem. Biol. Interact. 87, 425-430. 

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