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The amino functions of the common 2'-deoxyribo-and ribonucleosides were blocked by the (2-cyanoethoxy)carbonyl group on treatment with 2-cyanoethyl carbonochloridate (5) or 1-[(2-cyanoethoxy)carbonyl]-3-methyl-1H-imidazolium chloride (6) leading to 7, 18, 8, 19, 9, and 20. In 2'-deoxyguanosine, the amide group was additionally blocked at the O 6 position by the 2-cyanoethyl ( 3 27) and 2-(4-nitrophenyl)ethyl group ( 3 31, 32). Comparative kinetic studies regarding the cleavage of the ce/ceoc and npe/npeoc group by b-elimination revealed valuable information about the ease and sequential deprotection of the various blocking groups at different sites of the nucleobases. Besides the 5'guanosine analog 40 is recommended as building block for oligo-2'-deoxyribonucleotide synthesis. Introduction. ± The development of the 2-(4-nitrophenyl)ethyl (npe) and [2-(4-nitrophenyl)ethoxy]carbonyl (npeoc) groups as versatile protective groups for nucleobases [2], phosphate [3] [4], and phosphite functions [5] [6] broadened the strategy of nucleoside and nucleotide protection in oligonucleotide synthesis universally. The great advantange of these groups is their high stability under acidic and mild basic hydrolytic conditions as, for example, in the presence of ammonia and amines in MeOH, dioxane, or H 2 O, whereas their cleavage can easily and quantitatively be achieved by 1,8-diazabicyclo[5.4.0]undecene (DBU) in aprotic solvents by a b-elimination process.The 2-cyanoethyl (ce) group [7] [8] is the most common blocking group for the phosphate and phosphite moiety of nucleotides, but strangely enough, the ce and its corresponding (2-cyanoethoxy)carbonyl (ceoc) group have not been applied for base protection in analogy to the npe/npeoc couple. Several years ago, we [9] [10] developed the ce/ceoc strategy as an alternative approach for the synthesis of special oligonucleotides. Details about the nucleobase protection by the ce and ceoc group will now be reported since N-{[(2-cyanoethoxy)carbonyl]oxy}succinimide has recently been described as a new reagent for protection of amino groups in oligonucleotides [11]. We protected the amino group in cytidine, adenosine, and guanosine as well as in the corresponding 2'-deoxynucleosides with the ceoc group and utilized the ce group

59-77, are treated directly with 2-(4-nitrophenyl)ethylsulfonyl chloride forming in all cases a mixture of the 2',3'-di-U-and the two possible 2'-and 3'-0-monosulfonates 107-148 which can be separated into the pure components by chromatographic methods. The npes group is more labile towards DBU cleavage than the corresponding base-protecting 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) groups allowing selective deblocking which is of great synthetic potential.

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The b-heteroaryl-substituted ethanols 6 ± 10 were synthesized and, together with pyridine-2-ethanols and pyridine-4-ethanols, were tested as a new type of phosphate-protecting groups in the synthesis of oligonucleotides by the phosphotriester approach. The synthesis of 5'-O-(monomethoxytrityl)thymidine 3'-(bheteroarylethyl 2,5-dichlorophenyl phosphates) 13 ± 17 and 21 provided useful monomeric building blocks in which the various blocking groups could be removed selectively by acid (MeOTr), oximate (2,5-dichlorophenyl phosphate), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (heteroarylethyl phosphate) treatment. The new, fully blocked dimers 38 ± 41, with b-heteroarylethyl protecting groups in the phosphate moiety, were synthesized. The b-heteroarylethyl groups show a broad range of stability towards base treatment in aprotic solvents depending upon the activation of the HÀC(b) atoms by the heterocyclic moiety.1. Introduction. ± The use of b-eliminating phosphate-protecting groups can be regarded as an important improvement in phosphotriester chemistry [2] since cleavage of the phosphotri-to the phosphodiester stage will proceed without nucleophilic attack at the P-atom, avoiding a potential breakdown of the internucleotidic linkage. Among those protecting groups are the b-cyanoethyl (ce) group [3], the methyl-substituted bcyanoethyl groups [4], and the b-(alkylsulfonyl)-and b-(arylsulfonyl)ethyl groups [5]. Since these blocking groups are relatively sensitive to base treatment and eliminate already with ammonia and amines, a more stable type was found in the 2-(4-nitrophenyl)ethyl (npe) group [2a], which is inert towards amines but will be cleaved by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a much stronger base in a clean beliminating process. The npe group has proven its advantages in a series of oligonucleotide syntheses [6], which could be extended to a unified blocking-group strategy by introduction of the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group for base protection [7] and the 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) [8], the 2-(4-nitrophenyl)ethylsulfonyl (npes) [9], and the 2-(dansylethoxycarbonyl) (dnseoc) [10] groups for sugar-OH blocking. To broaden the spectrum of b-eliminating protecting groups for oligonucleotide chemistry, the use of N-containing heteroaryl residues has been tested as activators in b-elimination reactions [11]. Since an sp 2 -hybridized ring Natom reveals a similar activation power as a NO 2 group, the pyridinyl, pyrimidinyl, and pyrazinyl moieties were chosen as new entities in these investigations.