2J(P,C) and 3J(P,C) Coupling Constants in Some New Phosphoramidates. Crystal Structures of CF3C(O)N(H)P(O)[N(CH3)(CH2C6H5)]2 and 4‐NO2‐C6H4N(H)P(O)[4‐CH3‐NC5H9]2

Some new phosphoramidates were synthesized and characterized by ¹H, ¹³C, ³¹P NMR, IR spectroscopy and elemental analysis. The structures of CF₃C(O)N(H)P(O)[N(CH₃)(CH₂C₆H₅)]₂ ( 1 ) and 4‐NO₂‐C₆H₄N(H)P(O)[4‐CH₃‐NC₅H₉]₂ ( 6 ) were confirmed by X‐ray single crystal determination. Compound 1 forms a centrosymmetric dimer and compound 6 forms a polymeric zigzag chain, both via ‐N‐H…O=P‐ intermolecular hydrogen bonds. Also, weak C‐H…F and C‐H…O hydrogen bonds were observed in compounds 1 and 6 , respectively. ¹³C NMR spectra were used for study of ²J(P,C) and ³J(P,C) coupling constants that were showed in the molecules containing N(C₂H₅)₂ and N(C₂H₅)(CH₂C₆H₅) moieties, ²J(P,C)>³J(P,C). A contrast result was obtained for the compounds involving a five‐membered ring aliphatic amine group, NC₄H₈. ²J(P,C) for N(C₂H₅)₂ moiety and in NC₄H₈ are nearly the same, but ³J(P, C) values are larger than those in molecules with a pyrrolidinyl ring. This comparison was done for compounds with six and seven‐membered ring amine groups. In compounds with formula XP(O)[N(CH₂R)(CH₂C₆H₅)]₂, ²J(P,CH₂)_benzylic>²J(P,CH₂)_aliphatic, in an agreement with our previous study.     

Synthesis and properties of siRNAs containing 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides

Short interfering RNAs (siRNAs) containing P3′→N5′ phosphoramidate linkages were successfully synthesized by introducing 2′-deoxy-2′-fluororibonucleoside and 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleoside in succession. It was found that the introduction of 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides into siRNAs improved the nuclease-resistant properties of the siRNAs without loss of their silencing efficacy.     

Syntheses and molecular self-assembly of chiral phosphorami-dates

Two chiral phosphoramidates,(R)-(-)-1,1'-binaphthyl-2,2'-dihydroxy-N-[α-(S)-methylbenzyl] phosphoramidate and (-)-1,1'-biphenyl-2,2'-dihydroxy-N-[α-(S)-methylbenzyl]-phosphoramidate were synthesized.Their crystal structures were determined by X-ray single crystal diffraction analysis.The phosphoramidate molecules are self-associated by inter-molecular N-H...O = P hydrogen bonds and aromatic edge to face interactions.     

Synthesis and characteristics of sugar-phosphoramidates: A spectroscopic study

Phosphoramidate-incorporated scaffolds are structurally important targets owing to their diverse applications, particularly in medicinal chemistry. Herein we report the synthesis of several sugar phosphoramidates in excellent yields. NMR analyses were undertaken to examine their intramolecular H-bonding, stability under acidic conditions, and chemical shift effects.     

Synthesis and Resolution of Dinucleotide(TpAZT) Phosphoramidates

Abstract

Dinucleotide (TpAZT) phosphoramidates were synthesized through Atherton-Todd reaction of dinucleoside H-phosphonates and amino acid methyl esters, and their diastereomers (R_p and S_p) were separated by crystallization. It was showed that the cheap methyl esters of natural alanine and phenylalanine could act as new chiral auxiliaries for large-scale synthesis of dinucleotide analogs.     

Phosphorus-based combinatorial libraries: Use of amino acid derivatives as synthons

Summary Phosphorus has been used as a scaffold to prepare combinatorial libraries of phosphoramidates in which one of the diversity elements resulted from derivatives of amino acids. A small library was prepared for analytical and characterization purposes, followed by a larger library of approximately 8800 compounds. Libraries were assembled on solid supports using the conventional pool-and-divide method, followed by cleavage from the supports at the end of the synthesis. Mass spectrometry was used to confirm that library synthesis had been successful. Individual compounds were also prepared to study the stability of compounds of this type.     

Solid-phase synthesis of terminal oligonucleotide-phosphoramidate conjugates

A novel phosphoramidite, N,N-diisopropylamino-2-cyanoethyl-9-anthracenemethyl phosphoramidite 1, was prepared and coupled with the terminal 5′-hydroxyl of support-bound T₁₀ and the putative phosphite triester intermediate was subsequently reacted with iodine in the presence of either water or a series of primary and secondary amines. The reactivity of 1 compared to a previously reported benzyl phosphoramidite 2 was also investigated: oxidation of the product of coupling 2 with CPG-T₁₀-5′OH under aqueous conditions resulted in greater than 30% of the benzyl moiety being retained. In contrast, essentially complete loss of the 9-anthracenemethyl group was observed using 1 under the same conditions. Oligonucleotides modified with a terminal phosphate monoester, lipophilic, fluorescent or cationic groups were thus prepared.