Organic compounds of 2'-o-trisubstituted siloxy methyl ribonucleoside derivatives and their preparation

Abstract

The invention provides ribonucleoside derivatives with novel protecting groups and methods for the preparation of such ribonucleoside derivatives. The general formula (I) of the ribonucleoside derivatives is: wherein R1 is a base of the purine- or pyrimidine-family or a derivative of such a base or any other residue with serves as a nucleobase surrogate, R2 is a proton or a substituted derivative of phosphonic acid, R3 is a proton or a protection-group for the oxygen atom in 5'-position, R4, R5 and R6 are independently alkyl or aryl or a combination of alkyl and aryl or heteroatom, R4, R5 or R6 may also be cyclically connected to each other; and wherein at least one of the R4, R5 or R6 substituents comprises a tertiary C-atom or a heteroatom vicinal to the Si-atom.

Description

field of invention [0001] The invention belongs to the field of nucleic acid chemistry and relates to the preparation method and application of ribonucleoside derivatives with new protecting groups. The compounds of the invention are especially suitable for the automated preparation of oligoribonucleotides. Background of the invention [0002] Synthetic nucleic acids have many applications and are key to understanding biological processes. In these applications, the specific downregulation of proteins using synthetic oligonucleotides through specific hybridization to mRNA in cells is known as the antisense mechanism and has been extensively described (1). More recently, an RNA interference technique using dsRNA (termed siRNA) has been successfully used to inhibit the translation of mammalian mRNA into its protein (2). The great promise of RNA technology has created a need for the development of efficient and cost-effective synthetic oligoribonucleotide preparations. [00...

AI Technical Summary

Problems solved by technology

This 5' deprotection can be problematic in some cases: it requires a dedicated synthesizer resistant to fluoride ions and it is not possible to use commonly used silica-based supports (such as controlled pore glass)

For example, siloxymethyl groups (7) carrying a tertiary carbon located ortho to the Si atom have been reported, in these cases the yields of removal of the protecting group were not optimal compared to those usually observed with TBDMS protection, And obviously not suitable for the synthesis of solid-phase oligoribonucleotides

Images