organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
this in¯uences the duplex stability when (I) is a constituent of
a nucleic acid. Oligonucleotides containing 6-aza-20-deoxy-
uridine show a pH dependence on base-pair formation. The
lower pKa value of (I) causes problems during phosphor-
amidite synthesis. To circumvent this problem, various
protecting groups were introduced at the N3-position. The
o-anisoyl residue was found to be an ef®cient protecting group,
allowing multiple incorporations into the oligonucleotide
chain using phosphoramidite chemistry, with coupling yields
identical to those of standard phosphoramidites. These
properties prompted single-crystal analyses of (I) and its
N3-protected derivative, (II) (see scheme).
ISSN 0108-2701
6-Aza-20-deoxyuridine and N3-anisoyl-
6-aza-20-deoxyuridine
Frank Seela,a* Padmaja Chittepu,a Yang He,a Henning
Eickmeierb and Hans Reuterb
aLaboratorium fur Organische und Bioorganische Chemie, Institut fur Chemie,
È
È
Universitat Osnabruck, Barbarastrasse 7, 49069 Osnabruck, Germany, and
È
È
È
bAnorganische Chemie II, Institut fur Chemie, Universitat Osnabruck, Barbara-
È
È
È
strasse 7, 49069 Osnabruck, Germany
È
Correspondence e-mail: frank.seela@uni-osnabrueck.de
Received 10 November 2006
Accepted 15 January 2007
Online 17 February 2007
In 2-(2-deoxy-ꢀ-d-erythro-pentofuranosyl)-1,2,4-triazine-
3,5(2H,4H)-dione (6-aza-20-deoxyuridine), C8H11N3O5, (I),
the conformation of the glycosylic bond is between anti and
high-anti [ꢁ = 94.0 (3)ꢀ], whereas the derivative 2-(2-deoxy-
ꢀ-d-erythro-pentofuranosyl)-N4-(2-methoxybenzoyl)-1,2,4-
triazine-3,5(2H,4H)-dione (N3-anisoyl-6-aza-20-deoxyuridine),
C16H17N3O7, (II), displays a high-anti conformation [ꢁ =
86.4 (3)ꢀ]. The furanosyl moiety in (I) adopts the S-type
sugar pucker (2T3), with P = 188.1 (2)ꢀ and ꢂm = 40.3 (2)ꢀ,
while the sugar pucker in (II) is N (3T4), with P = 36.1 (3)ꢀ and
ꢂm = 33.5 (2)ꢀ. The crystal structures of (I) and (II) are
stabilized by intermolecular NÐHÁ Á ÁO and OÐHÁ Á ÁO inter-
actions.
6-Aza-20-deoxyuridine, (I), has an O40ÐC10ÐN1ÐC2
torsion angle ꢁ of 94.0 (3)ꢀ (IUPAC±IUB Joint Commission
on Biochemical Nomenclature, 1983) (Fig. 1 and Table 1),
which falls into the range of anti/high-anti conformations and
which is almost identical to that of the corresponding ribo-
nucleoside, (III), with ꢁ = 93.3ꢀ (Schwalbe et al., 1971;
Schwalbe & Saenger, 1973). The protected nucleoside, (II),
exhibits a high-anti conformation, with a torsion angle ꢁ of
86.4 (3)ꢀ (Fig. 2 and Table 3), and these values are similar to
those of other ortho-aza-nucleosides with an N atom next to
the glycosylation position, with ꢁ values close to 90ꢀ. This
results from the Coulombic repulsion between the non-
bonding electron pairs of atom O40 and the atom at position
N-6 in pyrimidine nucleosides or N-8 in 8-azapurine nucleo-
sides (8-aza-7-deaza-7-iodo-20-deoxyadenosine, with ꢁ =
106.3ꢀ; Seela et al., 1999). The glycosylic torsion angles of
related nucleosides, such as 6-aza-20-deoxythymidine (ꢁ =
86.6ꢀ; Banerjee & Saenger, 1978) and 6-aza-20-deoxy-5-
methylisocytidine (ꢁ = 103.4ꢀ; Seela et al., 2003), also lie in
the anti/high-anti range.
Comment
6-Azapyrimidine nucleosides show signi®cant antiviral activity
(Mitchell et al., 1986), while the N3-substituted derivatives
possess hypnotic and sedative properties and exhibit central
depressant effects in mice (Koshigami et al., 1991). 6-Aza-
uridine 50-monophosphate is a strong inhibitor of the enzyme
orotidine 50-monophosphate decarboxylase (Miller et al.,
2000), which, when linked to agarose, leads to an af®nity resin
used for the puri®cation of this enzyme (Rosemeyer & Seela,
1979). The ®rst synthesis of an anomeric mixture of 6-aza-20-
deoxyuridine was reported in 1963 (Pliml et al., 1963),
employing Hg derivatives of 6-azauracil and 2-deoxy-3,5-
di-O-(4-methylbenzoyl)-ꢃ-d-erythro-pentofuranosyl chloride.
Introducing an N atom at the 6-position of the pyrimidine
group has a profound effect on the physical and biological
properties of the nucleobase, which plays a signi®cant role in
the catalytic activity of ribozymes (Oyelere & Strobel, 2001)
and promotes M-DNA formation under neutral conditions
(Seela, Peng et al., 2005). The pKa value of (I) is 6.8 and that of
20-deoxyuridine is 9.5. Compared with these pKa values, the
6-azapyrimidine nucleoside is acidic and therefore it is already
deprotonated under neutral conditions. We have shown that
Figure 1
A perspective view of (I), showing the atomic numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level and H
atoms are shown as small spheres of arbitrary radii.
Acta Cryst. (2007). C63, o173±o176
DOI: 10.1107/S0108270107002016
# 2007 International Union of Crystallography o173
Seela, Frank
