M. Pfister et al., NUCLEOSIDES .59. THE 2-(4-NITROPHENYL)ETHYLSULFONYL (NPES) GROUP - A NEW-TYPE OF PROTECTION IN NUCLEOSIDE CHEMISTRY, Helvetica Chimica Acta, 78(7), 1995, pp. 1705-1737
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 beta-eliminating process under aprotic conditions u
sing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the most effective ba
se. Since sulfonates do not show acyl migration, partial protection of
1,2-cis-diol moieties is possible leading to new types of oligonucleo
tide building blocks. A series of Markiewicz-protected ribonucleosides
1-10 is converted into their 2'-0-[2-(4-nitrophenyl)ethylsulfonyl] de
rivatives 29-38 in which the 5'-O-Si bond can be cleaved by acid hydro
lysis forming 39-45. Subsequent monomethoxytritylation leads to 46-50,
and desilylation affords the -O-[2-(4-nitrophenyl)ethylsulfonyl]ribon
ucleosides 51-55. Acid treatment to remove trityl groups do also not h
arm the npes group (--> 56-58). Unambiguous syntheses of fully blocked
2'-O-[2-(4-nitrophenyl)ethylsulfonyl]rib 96-102 are achieved from the
corresponding 3'-O-(tert-butyl)dimethylsilyl derivatives. Furthermore
, various base-protected 5'-O-(monomethoxytrityl)- and 5'-O-(dimethoxy
trityl)ribonucleosides, i.e. 59-77, are treated directly with 2-(4-nit
rophenyl)ethylsulfonyl chloride forming in all cases a mixture of the
2',3'-di-0- and the two possible 2'- and 3'-O-monosulfonates 107-148 w
hich can be separated into the pure components by chromatographic meth
ods. The npes group is more labile towards DBU cleavage than the corre
sponding base-protecting 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitroph
enyl)ethoxycarbonyl (npeoc) groups allowing selective deblocking which
is of great synthetic potential.