HELVETICA CHIMICA ACTA -Val. 78 (1995) 1705 zy 126. Nucleosides Part LIX? The zyxwvu 2-(4-Nitrophenyl)ethylsulfonyl (Npes) Group zyx : A New Type of Protection in Nucleoside Chemistry by Magdalena Pfister, Helga Schirmeister, Marion Mohr, Silke Farkas, Klaus-Peter Stengele, Tilman Reiner, Martin Dunkel, Surendra Gokhale, Ramamurthy Charuhala, and Wolfgang Pfleiderer* Fakultat fur Chemie, Universitat Konstanz, Postfach 5560, D-78434 Konstanz Dedicated to my colleague Prof. Dr. zyxwvu R. R. zyxwvut Schmidt on the occasion of his 60th birthday (21.VI.95) 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 8-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 Murkiewicz-protected ribonucleosides zyxwvu 1-10 is converted into their 2’-0-[2-(4-nitrophenyl)ethylsulfonyl] derivatives 29-38 in which the Y-O-Si bond can be cleaved by acid hydrolysis forming 39-45. Subsequent niononiethoxytritylation leads to 46-50, and desilylation affords the 5 ’ 4 -(monornethoxytrityl)-2’-0-[2-(4-nitro- phenyl)ethylsulfonyl]ribonucleosides 51-55. Acid treatment to remove trityl groups do also not harm the npes group (+ zyxwvuts 56-58). Unambiguous syntheses of fully blocked 2’-0-[2-(4-nitrophenyl)ethylsulfonyl]ribonuc~eosides 96-102 are achieved from the corresponding 3’-0-(tert- buty1)dimethylsilyl derivatives. Furthermore, various base-protected 5’-0-(monomethoxytrity1)- and 5’-0-(dimethoxytrityl)ribonucleosides, zyxw i.e. 59-77, are treated di- rectly 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 chromato- graphic 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. 1. Introduction. - The chemical synthesis of oligonucleotides was tremendously im- proved in recent years by the development of the phosphoramidite approach which allows an automated build-up of oligodeoxyribonucleotides in a very efficient manner on different types of solid-support materials [2-71. More efforts, however, were put into the solution of an analogous methodology for the synthesis of oligoribonucleotides which gain more and more attention as antisense probes, modified ribozymes, and models for RNA-protein interactions as well as RNA structural studies. The additional 2’-OH group in the ribonucleoside series is responsible for the complexity of the applied strategy, since a special so-called permanent protecting group is needed which is, on one hand, stable enough to tolerate the manipulations during the synthetic cycles in assembling the ’) Part LVIII: [I].