Nucleotides. Part XXVII Bis[2-(p-nitrophenyl)ethyl] Phosphorochloridate, a New Versatile Phosphorylating Agent in Nucleotide Chemistry
✍ Scribed by Frank Himmelsbach; Ramamurthy Charubala; Wolfgang Pfleiderer
- Book ID
- 102859279
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- German
- Weight
- 628 KB
- Volume
- 70
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
A new, versatile phosphorylating agent, bis [2-0,-nitrophenyl)ethyl] phosphorochloridate (3), has been prepared and is used for 3'-and/or 5'-phosphorylations of nucleosides. The resulting bis[2-@-nitrophenyl)ethyl] phosphotriesters are versatile synthons in oligonucleotide synthesis leading finally to 3'-and/or 5'-terminated monophosphates in excellent yields.
Introduction. -Phosphorylations of nucleosides can be regarded as the most crucial point of any oligonucleotide synthesis performed by the phosphodiester and phosphotriester approach [2-51. Numerous phosphorylating agents have been proposed and are in use for this purpose and work quite satisfactorily depending upon the various substituents and activating functions. The normal procedures, however, are usually devised in this manner that the end products contain one more base residue than phosphate-ester group. Therefore, a more general method which is suitable for the introduction of phosphate groups at the 3'and 5'-ends of oligonucleotide chains is required. So far, the use of aryl phosphoroamido chloridates [6] and 0aryl S-methyl phosphorochloridothioates [7] has been recommended in this connection, but this still does not offer a simple solution of the problem due to some difficulties and potential side reactions in the final deprotection steps.
Recently, we have shown [S] that a new class of blocking groups based on substituted 2-phenylethanols offers some advantages over the commonly used protecting groups due to the relatively high stability under hydrolytic conditions and the easy and clean cleavage in aprotic solvents by a &elimination mechanism. We are in favour especially of the 2-(p-nitrophenyl)ethyl (Npe) and 2-(p-nitrophenyl)ethoxycarbonyl (NpeOCO) group [9] as universal, very versatile blocking groups in the phosphotriester approach offering a simple and unified protecting pattern.
An extension of this strategy is the development of a new phosphorylating agent, bis [2 (p -nitrophenyl)ethyl] phosphorochloridate (3) [lo], which exhibits the same structural features of high stability in the corresponding phosphotriester form and can, therefore, be carried along in the 3'-and/or 5'-position as a terminal function during the ') Part XXVI: [I] at 40"/0.2 Torr, 0.26 g (87%) ofan amorphous solid.