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The syntheses of new monomer building blocks for oligonucleotide synthesis via the phosphotriester approach containing the p-nitrophenylethyl group for phosphate and aglycone protection are described. Blocking of the amide function in guanosines at \{O6\} can be achieved by the Mitsunobu reaction forming the corresponding O6-p-nitrophenylethyl derivatives (4,5,10). Sugar-protected thymidine (16) and uridine (17) have been alkylated at \{O4\} in an SN1-type reaction by p-nitrophenylethyl iodide-silver carbonate in benzene to form the O4-p-nitrophenylethyl derivatives (18,19). Protection of the amino group in 2'-deoxycytidine (25) and cytidine (26) can be performed directly by 1-(p-nitrophenylethoxycarbonyl)-benzotriazole in \{DMF\} to obtain the corresponding carbamates (27,28) as a new type of N4-acylated cytidine derivative. p Nitrophenylethoxycarbonylation of the amino group in 2'-deoxyadenosine (33) and adenosine (34) requires previous sugar protection by acyl or silyl groups and can then be achieved by p-nitrophenylethyl chloroformate or better by 1-methyl-3-p-nitrophenylethoxycarbonylimidazolium chloride to form N6-p-nitrophenylethoxycarbonyladenosines (38,39,40,42). The various /-nitrophenylethyl blocking groups are stable under mild hydrolytic conditions (e.g. ammonia and triethylamine) but can be cleaved selectively by \{DBU\} or \{DBN\} in aprotic solvents. 5'-O-Monomethoxytritylation (12,29,43) as well as phosphorylations at the 3'-OH group can be effected to give the corresponding 3'-(2,5-dichlorophenyl,/-nitrophenylethyl)-phosphotriesters (13,22,30,44) also in high yields. Oximate cleavage of the latter compounds to the phosphodiesters (14,24,32,46) and detritylation to the 5'-unblocked phosphotriesters (15,23,31,45) do not affect the aglycone protecting groups, thereby demonstrating their general versatility. The newly synthesized compounds have been characterized on the basis of their elementary analyses (C, H, N), and UV- and 1H-NMR-spectra.
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