N.sup.4 -substituted 2'-deoxycytidine compounds, oligonucleotides including N.sup.4 -labeled 2'-deoxycytidines, and a process for making oligonucleotides with N-modified 2'-deoxycytidines

An oligonucleotide containing at least one modified nucleotide with a base of the formula:

• ##STR8## in which X is a linker containing between 1 and 18 carbon atoms inclusive;
• Y is --NH--;
• and
• W is a detectable reporter group with the proviso that the reporter group is not fluorescein.

A process for synthesizing an oligonucleotide which includes the repeated steps of joining a predetermined number of nucleoside via a phosphate bridge between their sugar moieties, wherein the improvement comprises using a modified nucleoside in at least one of the joining steps, said modified nucleoside having the formula ##STR9## in which X is a linker containing between 1 and 18 carbon atoms inclusive;

• Y is --NH--or N.dbd.;
• Z is N-formyl, N-acetyl, N-trichloroacetyl, N-trifluoroacetyl, N-o-nitrophenylacetyl, N-o-nitrophenoxyacetyl, N-acetoacetyl, N-3-phenylpropionyl, N-3(p-hydroxyphenyl)propionyl, N-2-methyl-2-(o-nitrophenoxy)propionyl, N-2-methyl-2-o-phenylazophenoxy)propionyl, N-4-chlorobutyryl, N-o-nitrocinnamoyl, N-picolinoyl, N-(N'-acetylmethionyl), N-benzoyl, N-phthaloyl, N-dithiasuccinoyl;
• N-methoxy carbamyl, N-9-fluorenylmethoxy carbamyl, N-2,2,2-trichloroethoxy carbamyl, N-2-trimethylsilylethoxy carbamyl, N-1,1-dimethylpropynoxy carbamyl, N-1-methyl-1-phenylethoxy carbamyl, N-1-ethyl-1-(4-biphenylyl)ethoxy carbamyl, N-1-1-dimethyl-2-haloethoxy carbamyl, N-1-1-dimethyl-2-cyanoethoxy carbamyl, N-t-butoxy carbamyl, cyclobutoxy carbamyl, N-1-methylcyclobutoxy carbamyl, N-1-adamantyloxy carbamyl, N-vinyloxy carbamyl, N-allyloxy carbamyl, N-cinnamyloxy carbamyl, N-8-quinolyloxy carbamyl, N-hydroxypiperidinyloxy carbamyl, N-4,5-diphenyl-3-oxazolin-2-one, N-benzyloxy carbamyl, N-p-nitrobenzyloxy carbamyl, N-3,4-dimethoxy-6-nitrobenzyloxy carbamyl, N-2-4-dichlorobenzyloxy carbamyl, N-5-benzisoxazolylmethoxy carbamyl, N-9-anthrymethoxy carbamyl, N-diphenylmethoxy carbamyl, N-isonicotinyloxy carbamyl, N-S-benzylthio carbamyl, N-(N'-phenylaminothiocarbonyl);
• N-allyl, N-phenacyl, N-3-acetoxypropyl, N-methoxymethyl, N-benzyloxymethyl, N-pivaloyloxymethyl, N-tetrahydropyranyl, N-2,4-dinitrophenyl, N-benzyl, N-o-nitrobenzyl, N-di(p-methoxyphenyl)methyl, N-triphenylmethyl, N-(p-methoxyphenyl) diphenylmethyl, N-diphenyl-4-pyridylmethyl, N-2-picolyl, N-isopropylidene, N-benzylidene, N-p-nitrobenzylidene, N-salicylidene, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl), N-NO.sub.2, N-diphenylphosphinyl, N-dimethylthiophosphinyl, N-benzenesulfenyl, N-o-nitrobenzenesulfenyl, N-2,4,6-trimethylbenzenesulfonyl, N-toluenesulfonyl, N-benzylsulfonyl, N-trifluoromethylsulfonyl, and N-phenacylsulfonyl;
• and
• each R.sub.1 and R.sub.2 is --OH, --SH, or --H;
• provided that at least one of R.sub.1 and R.sub.2 must be --OH or --SH.