Improved Process for the Preparation of Nucleosidic Phosphoramidites Using a Safer and Cheaper Activator

Sanghvi, Yogesh S.; Pfundheller, and Henrik M.; Converso, Antonella

doi:10.1021/op990086k

Cited by 49 publications

(38 citation statements)

References 21 publications

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“…The synthesis of the phosphoramidite 7 was carried out by phosphitylation of 6 with 2-cyanoethyl- N,N,N′,N′ -tetraisopropyl phosphoramidite and pyridinium trifluoroacetate as activator in high yield (31). The stability of phosphoramidite 7 was determined both in solution and as neat product.…”

Section: Resultsmentioning

confidence: 99%

Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose−Nucleoside Conjugates as Prodrugs

et al. 2010

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Phosphodiester linked conjugates of various nucleosides such as d4U, d4T, IdUrd, ddI, ddA, virazole, ara-A and ara-C containing a glucosyl moiety have been described. These compounds were designed to act as prodrugs, where the corresponding 5′-monophosphates may be generated intracellularly. The synthesis of the glycoconjugates was achieved in good yields by condensation of a glucosyl phosphoramidite 7 with nucleosides in the presence of an activating agent. It was demonstrated that the glucose-conjugates improve water solubility of the nucleoside analogues, for example up to 31-fold for ara-A conjugate compared to ara-A alone. The new conjugates were tested for their anti-HIV-1 activity in human lymphocytes. These derivatives offer a convenient design for potential prodrug candidates with the possibility to improve the physicochemical properties and therapeutic activity of nucleoside analogues.

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Section: Resultsmentioning

confidence: 99%

Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose−Nucleoside Conjugates as Prodrugs

et al. 2010

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“…1). We were pleased to discover that pyridinium trifluoroacetate is also effective in phosphitylation reactions [9], thus further minimizing potential for accidents in the synthesis of process raw materials.…”

Section: Use Of Pyridinium Trifluoroacetate As a Safer Activator Thanmentioning

confidence: 99%

Applications in Green Chemistry

Châtel¹

2016

Sonochemistry

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Abstract:We have modified the current phosphoramidite-based, solid-phase synthesis of antisense oligonucleotides to accommodate principles of green chemistry. In this article, we summarize key accomplishments that reduce or eliminate the use or generation of toxic materials, solvents, and reagents. Also discussed are methodologies that allow reuse of valuable materials such as amidites, solid-support, and protecting groups, thus improving the atom economy and cost-efficiency of oligonucleotide manufacture. Approaches to accident prevention and the use of safer reagents during oligonucleotide synthesis are also covered.

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“…[15] Synthesis of the high purity (>98.0%) CEP reagents 8a-c was completed by pyridinium trifluoroacetate-catalyzed condensation of the 3 -alcohol with 2-cyanoethyl-N,N,N ,N -tetraisopropyl phosphoramidite [16,17] and final purification by silica gel flash chromatography with degassed solvents. [18] For preparation of TPP reagents 10a-c (Figure 4), the 5 -O-DMTprotected nucleosides 7a-c were peracetylated with acetic anhydride in pyridine, followed by cleavage of the DMT and 4-N -acetyl protecting groups with 1,1,1,3,3,3-hexafluoro-2-propanol.…”

Section: Introductionmentioning

confidence: 99%