Phosphoramides, and

Both phosphoramidate and phosphate triester derivatives have been used as linkers to attach reporter groups to oligonucleotides. These derivatives are not entirely resistant to nucleases and they possess a chiral center. They have not been widely iavestigated as antisense dmgs. 

A series of N-allyl sulfamates, phosphoramides, and phosphorimidates was prepared to explore the possibility of O- N rearrangements via the intermediacy of the contact alkene radical cation/anion pair, followed by 5-exo-trigonal radical cyclizations (Fig. 4) [142],... 

The phosphoroiodidate decomposes on distillation, but evidence for its quantitative production in ethereal solution is obtained by its conversion in theoretical yield into the stable crystalline diethyl iV-phenyl phosphoramidate and aniline hydriodide by means of aniline ... 

Mechanistically, the compounds (162 X = O or S) and (163) represent two extremes in the base hydrolysis of phosphoramidates and phosphoramidothioates the former hydrolyse in an elimination-addition (EA) process whereas for the latter the sequence is one of addition followed by elimination AE). Further exploration of... 

The role of phosphoramidates and phosphazenes as 7V,0-ambident nucleophiles has been considered.79 Thus in the reaction of (EtO)3P=NCOPh with hydrogen chloride it appears that nitrogen rather than oxygen undergoes protonation ... 

In this review, we present asymmetric reactions catalyzed by stronger Brpnsted acids. The scope and limitations of chiral phosphoric acids, iV-triflyl phosphoramides, and dicarboxylic acids are described considering articles published until the middle of 2008. Although the mechanisms of a few transformations have been investigated in some detail, they are not the focus of this review. 

In 2006, Yamamoto and Nakashima picked np on this and designed a chiral A -triflyl phosphoramide as a stronger Brpnsted acid catalyst than the phosphoric acids based on this concept. In their seminal report, they disclosed the preparation of new chiral BINOL-derived A -triflyl phosphoramides and their application to the asymmetric Diels-Alder (DA) reaction of a,p-unsaturated ketones with sily-loxydienes [83], As depicted in Scheme 59, chiral A-triflyl phosphoramides of the general type 4 are readily synthesized from the corresponding optically active 3,3 -substituted BINOL derivatives 142 through a phosphorylation/amidation route. 

The study of the monoanions of a third class of phosphorus-containing monoesters, the phosphoramidates, has been restricted for the present to p- and o-substituted aryl phosphoramidates, and phosphoramidate and its O-methyl derivatives13-16. Two striking differences from the behavior of O- and S-phos-phate monoester monoanions are noted in the experimental criteria compiled in order to postulate mechanism (a) solvolysis in mixed organic solvents, particularly 50% v/v dioxan-water, results in a 50% decrease in the rate of hydrolysis of o- and p-substituted aryl phosphoramidate monoanions and all ionic forms of phosphoramidate and its O-methyl derivatives excepting the parent monoanion, and (b) partitioning of the aryl phosphoramidates and phos-... 

An obvious difficulty arises with this rather elaborate rationale when phosphoramidate and aryl phosphoramidate monoanions are compared for example, the dissimilarity of the dioxan effect yet the identity of product distribution observed in methanol-water competition experiments. Preliminary studies in the author s laboratory have revealed striking differences in the hydrolytic behavior between a series of phosphoramidafes derived from primary aliphatic amines and the above aryl systems. No linear structure-reactivity relationship between the logarithmic rate of hydrolysis of the monoanion species and the pKa of the amine is observed19. Moreover, the rate of hydrolysis of phosphoramidate monoanions derived from aliphatic amines is at least 104 times slower than those formed from aryl amines. In contrast, only a thirtyfold decrease in rate is observed for the corresponding ApKa in the O-phos-phate monoester series. The suspicion that mechanism (1), even with the above proposed modification, is not an accurate description of phosphoramidate monoanion hydrolysis derives some further support from the observation that the monoanion is subject to nucleophilic attack by substituted pyridines al-... 

Oligonucleotide phosphoramidates and other triplex-forming compounds may be designed to bind to specific DNA targets.1... 

T0 prepare models of TA, the corresponding cyclic alkylene phosphoric acids cannot be directly polymerized because the presence of acidic protons of the phosphate group makes the ionic polymerization impossible. Thus, cyclic phosphorus compounds with blocked third functions have to be used. These are phosphates., phosphoramidates and phosphites. After polymerization the obtained polymer is converted by deblocking into the polyalkylene phosphate, e.g. polysalt or polyacid form. 

Acidic proteinoid potentiates the active structure of lysine-rich proteinoid participating in forming microspheres in neutral buffer. Physical surface effects and providing micro condition in the microspheres could be surmised. Activation of amino acids generally requires acidic condition. Amino acids are activated by ATP and Mg2+ at pH 4-5 32 33). Aminoacyl adenylate anhydride and ester is formed preferentially from amino acid and adenylate imidazolide at pH 6.0J7). On the other hand, polycondensation of activated amino acids undergoes at pH values higher than 7. Peptides are formed from aminoacyl adenylate in basic buffer (the optimum pH is 10 for alanyl adenylate 40) from amino acid adenylate phosphoramidate and imidazole at pH 7.0 from N-(aminoacyl)-imidazole at pH 6-9 43). In this context, acidic and basic environments may be provided inside and/or on the surface of the microspheres composed of acidic and basic proteinoids in neutral buffer. Acidic micro condition suitable for the activation of amino acids and basic micro environment favorable for peptide formation from activated amino add may be provided. 

Metal Ion effect. Divalent metal ions (Mg2+, Co2+, Zn2+, Ni2+) catalyzed the above nucleophilic reaction on the phosphorus atom. The yields of phosphoramidate and inorganic sulfate become 100% in the presence of Mg2+ ion. In Figure 7 are shown the effect of Mg2+ ion on the reaction of imidazole. In this case, imidazole acts as nucleophilic catalyst. The figure shows that the kohs values tend to deviate from the first-order dependency on Mg2+ ion at high metal ion concentration, suggesting the complexation of substratje with metal ion. 

A one-pot procedure for the activation and metalation of tetrahydroisoquinoline involves the carbona-tion of tie li ium amide anion and then further metalation. As is illustrated in Scheme 45, the dipole-stabilized anion species may be added to carbonyl compounds in good yield.For the activation of tetrahydroisoquinoline Grignards, Seebach examined benzamides, pivalamides and phosphoramides, and found that the benzamides would not metalate, and that although the phosphoramides were most easily removed, the pivalamides were the most nucleoj ilic species. As is shown in Scheme 46, the lithiated pi-valoylisoquinoline adds to cyclohexanone in good yield. 

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