Patent ID: 6187914
Filing Date: 2001-02-13
Classification: C07H

Abstract:
A method of oligonucleotide synthesis, comprising:successive adding nucleotides starting with a first nucleoside attached to a solid support, wherein each addition of a nucleotide comprises the cleavage of the protecting group for the 5'-OH function of the nucleotide or of the preceding nucleoside, and the coupling of the nucleotide to be added, to the deprotected 5'-OH function,wherein at least one of addition of a nucleotide is carried out with a nucleoside derivative represents by the formula (I), and wherein the cleavage of the protecting group for the 5'-OH function of the nucleotide represented by formula (I) is carried out by an electrochemical reaction, ##STR9##whereinR.sub.1 represents:an electrolabile group represented by formula (IIa): ##STR10##in which R.sub.4 represents an NO.sub.2 group and R.sub.5 represents a hydrogen atom, a linear or branch C.sub.1 to C.sub.10 alkyl group, a group ##STR11##or a group ##STR12##where R' represents a linear or branched C.sub.1 to C.sub.10 alkyl group, or a group --O--R' where R' represents a linear or branched C.sub.1 to C.sub.10 alkyl group, or alternativelyan electrolabile group represented by formula (IIb): ##STR13##in which one of the groups Ra, Rb or Rc represents a phenyl group, or a substituted phenyl group, and the other two represent hydrogen atoms,R.sub.2 represents a hydrogen atom, or a phosphoramidite, phosphonate or phosphotriester group;R.sub.3 represents a hydrogen atom, a hydroxyl radical, a substituted hydroxyl radical or a halogen,B represents a radical derived from a purine or a pyrimidine base represented by one of the following formulae: ##STR14##wherein R.sub.6 represents a protecting group for the amine function, other than an isobutyryl or phenylpropionyl group, represented by one of the formulae (VII), (VIII) or (IX) below: ##STR15##in which R.sub.9 and R.sub.11, which may be identical or different, represent a hydrogen atom, or a C.sub.1 -C.sub.10 alkoxy or alkyl group, R.sub.12 represents a linear or branched C.sub.1 -C.sub.10 alkyl radical, and R.sub.10 is represented by the formula: ##STR16##R.sub.7 represents a protecting group for the amine function, other than a phenylpropionyl group, represented by one of the formulae (VII), (VIII) or (IX) defined above;R.sub.8 represents a protecting group for the amine function, other than an isobutyryl, phenylpropionyl or phenoxyacetyl group, corresponding to one of the formulae (VII), (VIII) or (IX) defined above;with the exception of the derivatives in which R.sub.1 is an electrolabile group represented by formula (IIa) in which R.sub.4 represents an NO.sub.2 group and R.sub.5 a hydrogen atom, and B is represented by formula (III).