Process for 5'-phosphorylation of nucleic acids

Claim 1

A process for the preparation of compounds of the formula I ##STR19## in which Kat represents one molar equivalent of a cation, R is an organic radical which carries no further phosphorylatable hydrogen atoms, X represents oxygen, sulfur or selenium, X represents oxygen, sulfur or --NH-- and n is 1 to 6, which comprises reacting in the presence of weak acid, a compound of the formula II R--(Z--H).sub.n II with at least n moles of the phosphorylating reagent of the formula III ##STR20## in which R 1 represents a group of the formula IIIa or IIIb ##STR21## R 5 , R 6 and R 7 , which can be identical or different, denote hydrogen or methyl, R 8 denotes of the formula IIIc, IIId, or IIIe or cyano or Ar, ##STR22## R 10 denotes lower alkyl or Ar, G, which can be identical or different, denotes C or N, but at least one G represents N, Ar denotes phenyl which can be substituted by 1 to 5 identical or different substituents belonging to the series chlorine, fluorine, nitro and cyano or, in addition to the election-withdrawing substituents, can be substituted by branched or unbranched alkyl with 8 to 24 carbon atoms y is 0, 1 or 2, R 9 denotes a group of the formula IIIf or IIIg ##STR23## Y denotes identical or different substituents belonging to the series chlorine, bromine or iodine, R 2 can have a meaning of R 1 and is then identical or different, or denotes lower alkyl, a group of the formula IIIh --CH.sub.z --Ar IIIh or Ar, if the latter can be removed by alkaline hydrolysis at a higher rate, under alkaline conditions, than R 1 by alkalis, R 5 and R 8 together represent a group of the formula IIIi ##STR24## and R 1 also represents methyl if R 2 is also methyl, and R 3 and R 4 , which can be identical or different, denote alkyl having 1 to 8 carbon atoms, cycloalkyl having 5 to 12 carbon atoms, benzyl or phenyl or, together with the nitrogen atom to which they are attached, denote a saturated or unsaturated heterocyclic ring which can contain further heteroatoms and substituents, oxidizing the resulting compound of the formula IV ##STR25## in which R 1 , R 2 , R, Z and n have the meanings mentioned and liberating the compound of the formula I by means of bases from the oxidized compounds of the formula V ##STR26## in which n, R 1 , R 2 , X, Z and R have the meanings mentioned.