Nucleotides, Part LXVII, The 2-Cyanoethyl and (2-Cyanoethoxy)carbonyl Group for Base Protection in Nucleoside and Nucleotide Chemistry

Abstract

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 O6 position by the 2-cyanoethyl (→27) and 2-(4-nitrophenyl)ethyl group (→31, 32). Comparative kinetic studies regarding the cleavage of the ce/ceoc and npe/npeoc group by β-elimination revealed valuable information about the ease and sequential deprotection of the various blocking groups at different sites of the nucleobases. Besides the 5′-O-(dimethoxytrityl)-protected 3′-(2-cyanoethyl diisopropylphosphoramidites) 38 and 39 of N4-[(2-cyanoethoxy)carbonyl]-2′-deoxycytidine and N6-[(2-cyanoethoxy)carbonyl]-2′-deoxyadenosine, respectively, the N2-[(2-cyanoethoxy)carbonyl]-2′-deoxy-O6-[2-(4-nitrophenyl)ethyl]guanosine analog 40 is recommended as building block for oligo-2′-deoxyribonucleotide synthesis.