Nucleosides. Part LIX. The 2-(4-nitrophenyl)ethylsulfonyl (Npes) group: A new type of protection in nucleoside chemistry

Article abstract of DOI:10.1002/hlca.19950780706

The 2-(4-nitrophenyl)ethylsulfonyl (npes) group is developed as a new sugar OH-blocking group in the ribonucleoside series. Its cleavage can be performed in a β-eliminating process under aprotic conditions using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the most effective base. Since sulfonates do not show acyl migration, partial protection of 1,2-cis-diol moieties is possible leading to new types of oligonucleotide building blocks. A series of Markiewicz-protected ribonucleosides 1-10 is converted into their 2'-O-[2-(4-nitrophenyl)ethylsulfonyl] derivatives 29-38 in which the 5'-O-Si bond can be cleaved by acid hydrolysis forming 39-45. Subsequent monomethoxytritylation leads to 46-50, and desilylation affords the 5'-O-(monomethoxytrityl)-2'-O-[2-(4-nitrophenyl)ethylsulfonyl]ribonucl eosides 51-55. Acid treatment to remove trityl groups do also not harm the npes group(→ 56-58). Unambiguous syntheses of fully blocked 2'-O-[2-(4-nitrophenyl)ethylsulfonyl]ribonucleosides 96-102 are achieved from the corresponding 3'-O-(tert-butyl)dimethylsilyl derivatives. Furthermore, various base-protected 5'-O-(monomethoxytrityl)- and 5'-O-(dimethoxytrityl)ribonucleosides, i.e. 59-77, are treated directly with 2-(4-nitrophenyl)ethylsulfonyl chloride forming in all cases a mixture of the 2',3'-di-O- and the two possible 2'- and 3'-O-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.