Nucleosides. Part LIX. The 2‐(4‐nitrophenyl)ethylsulfonyl (Npes) Group: A New Type of Protection in Nucleoside Chemistry

Abstract

AbstractThe 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]ribonucleosides 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.