160636-25-9Relevant academic research and scientific papers
Improved process for the preparation of nucleosidic phosphoramidites using a safer and cheaper activator
Sanghvi, Yogesh S.,Guo, Zhiqiang,Pfundheller, Henrik M.,Converso, Antonella
, p. 175 - 181 (2000)
A new, simplified commercial process for the preparation of nucleosidic phosphoramidites, key raw materials for the automated solid-supported synthesis of oligonucleotide-based drugs, was developed. Phosphitylation of a variety of protected nucleosidic derivatives (1-4) with a small excess of 2-cyanoethyl-N,N,N′,N′-tetraisopropyl phosphoramidite (5, bis-reagent) and pyridinium trifluoroacetate (Py·TFA) as the activator in an appropriate solvent at room temperature formed 75-96% of desired nucleosidic phosphoramidite products in less than 2 h. An efficient nonaqueous work-up has been developed to further streamline the isolation of moisture-sensitive P(III) nucleosidic compounds. The key finding is the use of Py·TFA, which is effective, inexpensive, stable, less acidic (pKa 5.2) than 1H-tetrazole, nontoxic, safe, and highly soluble in organic solvents. The reaction mechanism for phosphitylation with Py TFA as an activator has also been studied. An improved, robust, and versatile process for the preparation of nucleotide phosphoramidites under very concentrated reaction conditions was developed to support commercial manufacture of oligonucleotide-based drugs.
ON-DEMAND PHOSPHORAMIDITE SYNTHESIS
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Page/Page column 36-38; 48, (2022/01/24)
The invention relates to a method of synthesis of phosphoramidites by immobilization of a phosphitylation agent on a resin activated to create a charged resin, then putting in contact with the charged resin with a suitable substrate. Phosphoramidites are synthesized in a few minutes from the application of the starting materials. Thus, the process makes it possible to create specific phosphoramidites on demand when they are needed in other applications. The substrates to be applied are mainly nucleosides, thus making it possible to create nucleoside phosphoramidites for the subsequent synthesis of oligonucleotides.
Process for the preparation of 2'-O-alkyl purine phosphoramidites
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, (2016/06/29)
2'-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3'-O-phosphoramidites are prepared by alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. Alkylation is effected on 2,6-diamino-9-(β-D-ribofuranosyl)purine followed by deamination to prepare guanosine 2'-O-alkylated 3'-O-phosphormidites. Alkylation is effected on a dialkyl stannylene derivative of uridine to prepare uridine 2'-O-alkylated 3'-O-phosphormidites. Alkylation is effected directly on cytidine to prepare cytidine 2'-O-alkylated 3'-O-phosphormidites. Alkylation is effected directly on 2,6-diaminopurine to prepare 2,6-diaminopurine 2'-O-alkylated 3'-O-phosphormidites.
