7-Iodo-5-aza-7-deazaguanine: Syntheses of anomeric D- and L-configured 2-deoxyribonucleosides

Article abstract of DOI:10.1002/hlca.200490201

Iodination of N²-isobutyryl-5-aza-7-deazaguanine (7) with N-iodosuccinimide (NIS) gave 7-iodo-N²-isobutyryl-5-aza-7- deazaguanine (8) in a regioselective reaction (Scheme 1). Nucleobase-anion glycosylation of 8 with 2-deoxy-3,5-di-O-

Full text of DOI:10.1002/hlca.200490201

Helvetica Chimica Acta Vol. 87 (2004)
2235
7-Iodo-5-aza-7-deazaguanine: Syntheses of Anomeric d- and l-Configured
2-Deoxyribonucleosides
by Wenqing Lin, Xiaomei Zhang, and Frank Seela*
Laboratorium f¸r Organische und Bioorganische Chemie, Institut f¸r Chemie, Universit‰t Osnabr¸ck,
Barbarastrasse 7, D-49069 Osnabr¸ck
and
Center for Nanotechnology (CeNTech), Gievenbecker Weg 11, D-48149 M¸nster
Iodination of N2-isobutyryl-5-aza-7-deazaguanine (7) with N-iodosuccinimide (NIS) gave 7-iodo-N2-
isobutyryl-5-aza-7-deazaguanine (8) in a regioselective reaction (Scheme 1). Nucleobase-anion glycosylation of
8 with 2-deoxy-3,5-di-O-toluoyl-a-d- or a-l-erythro-pentofuranosyl chloride furnished anomeric mixtures of d-
and l-nucleosides. The anomeric d-nucleosides were separated by crystallization to give the a-d-anomer and b-
d-anomer with excellent optical purity. Deprotection gave the 7-iodo-5-aza-7-deazaguanine 2'-deoxyribonu-
cleosides 3 (b-d; ꢀ 99% de) and 4 (a-d; ꢀ 99% de). The reaction sequence performed with the d-series was
also applied to l-nucleosides to furnish compounds 5 (b-l; ꢀ 99% de) and 6 (a-l; ꢀ 95% de).
Introduction. The 5-aza-7-deazapurines (imidazo[1,2-a]-1,3,5-triazines) display a
shape similar to that of the parent purines. In the series of guanine nucleoside analogs,
e.g., in nucleoside 1 with the imidazole N-atom in the bridgehead position 5, the
donorÀacceptor pattern of the −pyrimidine× as well as the imidazole moiety changes [1]
(purine numbering is used throughout the discussion). The absence of N(7) in 1
prevents Hoogsteen base-pair formation, and N(1) is no longer a proton donor but acts
as proton acceptor. As a consequence, 5-aza-7-deazaguanine shows the base-pair-
recognition properties of isocytidine. Thus, stable base pairs can be formed with
guanine or isoguanine resulting in duplexes with parallel or antiparallel chain
orientation [2][3]. As the chain orientation can be changed not only by alteration of
the nucleobase donorÀacceptor pattern but also by the configuration at the anomeric
center of the nucleoside, compounds 1 and 2 form duplexes with opposite chain
orientations [4]. Meanwhile, 5-aza-7-deazaguanine and its nucleosides and nucleotides
have been shown to develop antiviral activity, especially against rhino viruses, herpes-
simplex virus type I and herpes simplex virus type II [5]. The 5-aza-7-deazaguanine can
also act as inhibitor of xanthine oxidase [6] and its 2',3'-dideoxyribonucleoside
triphosphate has the potential to inhibit HIV reverse transcriptase [7].
Earlier, 7-halogenated 7-deazapurine and 8-aza-7-deazapurine (ˆ pyrrolo[2,3-d]-
pyrimidine and pyrazolo[3,4-d]pyrimidine, resp.) nucleosides have been incorporated
into DNA either chemically or enzymatically [8 16]. By this means, oligonucleotide
duplexes became stabilized. Moreover, the iodinated compounds have been subjected
to the Sonogashira cross-coupling reaction, which allowed the introduction of side
chains into the molecules [17]. As we want to extend our studies on 5-aza-7-
deazapurine nucleosides and oligonucleotides with various substituents at position 7
¹ 2004Verlag Helvetica Chimica Acta AG, Z¸rich

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Helvetica Chimica Acta Vol. 87 (2004)
from the d-series to those with l-configuration [18 21], this communication reports
the synthesis of the iodinated d-nucleosides 3 and 4 as well as of the corresponding l-
enantiomers 5 and 6. According to earlier work, the glycosylation of 5-aza-7-
deazaguanine always results in the formation of anomeric mixtures [5]. Thus, an
effective separation had to be developed to allow large-scale preparation and avoid
chromatography, which is unsuccessful in this series of nucleosides.
Results and Discussion. First, 5-aza-7-deazaguanine was isobutyrylated in the
presence of isobutyric anhydride/phosphoric acid to give N2-isobutyryl-5-aza-7-
deazaguanine (7) as previously described [5]. Compound 7, which is much better
soluble than its nonprotected precursor, was anticipated to undergo regioselective
halogenation as was observed with pyrrolo[2,3-d]pyrimidines [22 25]. Treatment of 7
with N-iodosuccinimide (NIS) in anhydrous CH2Cl2 (room temperature) furnished 7-
iodo-N2-isobutyryl-5-aza-7-deazaguanine (8) as a single isomer in 35% yield
(Scheme 1). No desired product was obtained with NIS in anhydrous DMF or with
iodomonochloride (ICl) in aqueous AcONa solution. We failed to improve the yield,
Scheme 1

Helvetica Chimica Acta Vol. 87 (2004)
2237
probably due to an oxidative destruction of 7 or of its reaction product 8. The site of
iodination was determined by NOE difference spectra and gated-decoupled 13C-NMR
spectra of compound 3 (see below).
Compound 8 was glycosylated according to our previously described procedure [5].
Thus, 2-deoxy-3,5-di-O-toluoyl-a-d-erythro-pentofuranosyl chloride was prepared
according to Hoffer [26] and Kotera and co-workers [27] and was employed in the
glycosylation of 8 in the presence of potassium carbonate and tris[2-(2-methoxyethox-
y)ethyl]amine (TDA) to give a colorless foam in 95% yield (Scheme 2). This foam was
1
a mixture of the b-d and a-d-anomers 9 and 10 as shown by H-NMR and reversed-
phase HPLC. As expected, attempts to separate the anomers 9/10 by column
chromatography failed. Therefore, the mixture 9/10 was deprotected with NH3/MeOH
to furnish the anomer mixture 3/4. Nevertheless, this mixture could not be separated by
column chromatography either. Later, the anomer mixture of 3/4 was silylated, and the
reaction products were separated by column chromatography according to a protocol
described for the separation of 2',3'-dideoxy-5-aza-7-deazaguanosine [1]. Unfortu-
nately, the purification of 3 and 4 was laborious, and pure 3 and 4 could not be obtained
even by repeated column chromatography.
Scheme 2
Since the anomer mixtures 9/10 and 3/4 could not be separated chromatograph-
ically, we had to search for another method of separation. When the anomer mixture
9/10 was dissolved in hot MeOH, only the b-d-anomer 9 crystallized upon cooling. The
solvent of the mother liquid was then removed and the a-d-anomer 10 was
recrystallized from AcOEt/petroleum ether (60 808). Then, 9 and 10 were depro-
tected separately in saturated NH3/MeOH solution to furnish the nucleosides 3 and 4 in
92 and 95% yield, respectively (Scheme 3). Both nucleosides were of excellent optical
purity (ꢀ 99% de), as determined by reversed-phase HPLC (RP-18 column, phosphate
buffer (pH 7.2)/MeCN 95 :5, 0.7 ml/min; tR 27 (b-d-anomer) and 29 min (a-d-
anomer)).

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 3
The anomer configurations of 3 and 4 were confirmed by NOE difference spectra (Table 1). Irradiation of
HÀC(1') of nucleoside 3 resulted in an NOE at HaÀC(2') of 4.2% and at HÀC(4') of 3.4%, which demonstrates
that HÀC(1'), HaÀC(2'), and HÀC(4') are on the same side of the sugar ring; thus, 3 was assigned to be the b-d-
anomer. Irradiation of HÀC(1') of 4 resulted in an NOE at HbÀC(2') of 1.0% and at HÀC(3') of 1.2%; thus, 4
was assigned to be the a-d-anomer. According to the configurational assignments of 3 and 4, compounds 9 and
10 were assigned accordingly.
When HÀC(1') of 3 was irradiated, an NOE of 6.0% was observed at HÀC(8) (Table 1). Thus, the I-atom
was selectively introduced at C(7) of 8 (see above). The 13C-NMR spectrum of nucleoside 3 (Table 2) shows a
resonance of the nucleobase at d(C) 120.9 splitting into four signals (dds with 1J ˆ 203.80 Hz and 3J ˆ 3.96 Hz).
This reveals that this C-atom is bonded to a proton and that there is another proximal proton, i.e., C(8) shows
couplings with HÀC(8) (1J ˆ 203.80 Hz) and HÀC(1') (3J ˆ 3.96 Hz).

Helvetica Chimica Acta Vol. 87 (2004)
2239
a
Table 1. NOE Data and Conformation of Nucleosides 3
6 )
Proton irradiated NOE observed [%]
HÀC(1') HbÀC(2') HaÀC(2') HÀC(3') HÀC(4') HÀC(8)
anti [%]
3
4
HÀC(8)
HÀC(1')
HÀC(8)
HÀC(1')
HÀC(8)
HÀC(8)
HÀC(1')
1.1
3.7
1.1
52
47
4.2
3.1
3.4
1.5
6
1.2
1
4.6
1.2
1.0
2.4
5
6
1.3
0.7
60
53
3.3
1.7
4.5
1.7
4.8
a) Measured in (D6) DMSO at 303 K.
Encouraged by the success in separating the anomer mixture 9/10, compound 8 was
glycosylated with 2-deoxy-3,5-di-O-toluoyl-a-l-erythro-pentofuranosyl chloride, which
was prepared according to the procedure for the d-sugar [26 28]. The obtained
mixture 11/12 of b-l- and a-l-anomers was crystallized from MeOH to afford the b-l-
anomer 11 (Scheme 4). From the mother liquor, the a-l-anomer 12 was obtained by
crystallization from AcOEt/petroleum ether. Removal of the toluoyl and isobutyryl
groups from 11 and 12 resulted in 5 and 6, respectively, which was accomplished in NH3/
MeOH at room temperature. The nucleosides 5 and 6 were of excellent optical purity
(ꢀ 99 and ꢀ 95% de, resp.), as determined by reversed-phase HPLC (RP-18 column,
phosphate buffer (pH7.2)/MeCN 95 :5, 0.7 ml/min; tR 27 (l-b-anomer and 29 min (a-l-
anomer). The configurations of 11, 12, 5, and 6 were assigned as described for the d-
compounds and were in full agreement with the data expected (Table 1).
Scheme 4

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Helvetica Chimica Acta Vol. 87 (2004)

Helvetica Chimica Acta Vol. 87 (2004)
2241
No significant difference of the pK values of protonation between compound 3
(pKa ˆ 3.6) and the nonhalogenated 1a (pKa ˆ 3.7) [5] was observed by pH-dependent
UV spectra [29]. The UV maximum of the compounds 3 6 (lmax 265 nm, pH 7) show a
small red shift compared to the noniodinated 1a (lmax 257 nm, pH 7).
The conformation of the 5-aza-7-deazaguanine relative to the sugar moiety can be
calculated from a calibration graph according to the NOE data of Table 1 [30]. No
significant difference was observed among the conformation of 3 6. The anti-
conformation populations of 3 6 are 52, 47, 60, and 53%, respectively. Next, the N $ S
pseudorotational equilibrium of the sugar moiety was determined. The 1H-NMR
3
spectra of compound 3 6 were measured in D2O, J(H,H) coupling constants were
determined (Table 3). The conformational analysis was performed with the program
PSEUROT [31]. As can be seen from Table 3, compounds 3, 5, and 1a (b-anomers)
show the same population of S-conformers (62 63%); compounds 4, 6, and 2 (a-
anomers) show significantly higher populations of the S-conformers (76 79%). The
conformational differences between the b- and a-anomers result from differences of
the anomeric effect caused by the base, which is favorable to N-conformation in b-
anomers and favorable to S-conformation in series of a-anomers. The conformation of
the exocyclic C(4')ÀC(5') bond of 3 6 were calculated based on J(4',5'a) and J(4',5'b)
according to Westhof et al. [32]. Compounds 1a, 2, and 3 6 show similar population of
the gauche,gauche-conformation. Thus, it can be concluded that the iodo substituent
does not have a significant influence on the conformation of the sugar puckering as well
as of the C(4')ÀC(5') bond.
Table 3. 1H-NMR Coupling Constants J(H,H) [Hz] and Conformation of the Nucleosides 1 6 a)
3
Conformation
J(1',2'a) J(1',2'b) J(2',3') J(2'b,3') J(3',4') J(4',5'a) J(4',5'b) %N %S gg‡ gt
ggÀ
1a[2]
2[5]
3
4
5
6
37
22
38
21
38
24
63
78
62
79
62
76
48
33 19
6.55
7.41
6.51
7.42
6.55
2.56
6.51
2.61
6.38
6.86
6.33
6.88
4.22
2.71
4.14
2.61
3.88
3.22
3.89
3.21
3.71
3.71
3.69
3.73
5.07
5.17
5.07
5.20
47
46
48
46
34 19
35 19
34 18
35 19
a) Measured in D2O at 303 K.
Finally, the CD spectra of compounds 3 6 were measured; they show mirror-like
curves for the d- and l-series. Compound 3 (b-d) exhibits negative Cotton effects
around 275 and 228 nm and 5 (b-l) positive ones at the same wavelengths. Similarly, 4
(a-d) gives rise to a positive Cotton effect around 275 nm and to a negative one around
235 nm; compound 6 (a-l) exhibits the opposite behavior.
In conclusion, we successfully accomplished the regioselective introduction of a
iodo substituent in a 5-aza-7-deazaguanine nucleoside and developed a simple and
convenient practical procedure to separate the a- and b-anomer mixtures both in the d-
and the l-series of the nucleosides. The separated anomeric 2-deoxy-d-ribonucleosides
of 7-iodo-5-aza-7-deazaguanine were obtained in ꢀ 99% de, and the b- and a-anomers
of the 2-deoxy-l-ribonucleosides in ꢀ 99 and ꢀ 95% de, respectively. Studies on the

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Helvetica Chimica Acta Vol. 87 (2004)
biological activities and base-pairing properties in duplex DNA are under investiga-
tion.
We are grateful to Dr. Helmut Rosemeyer for helpful discussions and for measuring the NMR spectra. We
also acknowledge the support by Mrs. M. Dubiel, Mrs. Eva-Maria Becker, Mrs. Elisabeth Michalek, and Dr. Peter
Leonard. The work was financially supported by the European Community (Grant No.: QLRT-2001-00506,
−Flavitherapeutics×).
Experimental Part
General. Solvents: technical grade, distilled before use. Flash chromatography (FC): 0.4bar, silica gel 60 H
(VWR, Darmstadt, Germany). TLC: aluminium sheet, silica gel 60 F254 (0.2 mm; VWR, Germany). UV
Spectra: U3200 spectrophotometer (Hitachi, Japan). NMR Spectra: Avance-DPX-250 spectrometer or AMX-
500 spectrometer (Bruker, Rheinstetten, Germany), at 250.13 and 500 MHz for 1H and 62.90 and 125.13 MHz
for 13C; d values in ppm rel. to internal SiMe4 (1H,13C). CD Spectra: Jasco-600 instrument (Jasco, Japan); at r.t.
Microanalyses were performed by Mikroanalytisches Labor Beller (Gˆttingen, Germany). Chemicals were
purchased from Acros, Fluka, or Sigma-Aldrich.
N-(4,8-Dihydro-6-iodo-4-oxoimidazo[1,2-a]-1,3,5-triazin-2-yl)-2-methylpropanamide (8). To the stirred
suspension of N-(4,8-dihydro-4-oxoimidazo[1,2-a]-1,3,5-triazin-2-yl)-2-methylpropanamide (7;
4 .0 g,
18.08 mmol) [6] in anh. CH2Cl2 (400 ml) was added N-iodosuccinimide (4.5 g, 20.00 mmol) in one portion at
r.t. Stirring was continued for 30 min and the solvent evaporated. The residue was applied to FC (silica gel,
CH2Cl2/MeOH 100 :2): 8 (2.2 g, 35%). Yellowish powder. TLC (silica gel, CH2Cl2/MeOH 20 :1): Rf 0.24. UV
(MeOH): 295 (10200). 1H-NMR ((D6)DMSO): 1.10 (s, 2 Me); 2.75 (m, CH); 7.31 (s, HÀC(7)); 11.47, 12.00 (2s,
2 NH). Anal. calc. for C9H10IN5O2 (347.11): C 31.14, H 2.90, I 36.56; N 20.18; found: C 31.28, H 3.03, I 36.50, N
20.25.
N-{8-[2-Deoxy-3,5-di-O-(p-toluoyl)-d-erythro-pentofuranosyl]-4,8-dihydro-6-iodo-4-oxoimidazo[1,2-a]-
1,3,5-triazin-2-yl}-2-methylpropanamides (9/10). Compound 8 (2.36 g, 6.80 mmol) was dissolved in hot MeCN
(200 ml), then K2CO3 (3.0 g, 21.7 mmol) and TDA (0.3 ml, 0.94mmol) were added under stirring. Stirring was
continued at r.t. for 15 min. Then 2-deoxy-3,5-di-O-toluoyl-a-d-erythro-pentofuranosyl chloride (4.2 g,
10.80 mmol) was added, and stirring was continued for 1.5 h. The mixture was filtered, the filtrate evaporated,
and the residue subjected to FC (silica gel, CH2Cl2/MeOH 500 :1): 9/10 (4.5 g, 95%). Yellowish foam. TLC
(silica gel, CH2Cl2/MeOH 200 :1): Rf 0.23 (one spot).
2-Amino-8-(2-deoxy-d-erythro-pentofuranosyl)-6-iodoimidazo[1,2-a]-1,3,5-triazin-4-(8H)-ones (3/4). A
mixture 9/10 (0.33 g, 0.47 mmol) in NH3/MeOH (50 ml) was stirred at r.t. for 2 days. The mixture was
evaporated and the residue applied to FC (silica gel, CH2Cl2/MeOH 20 :1 ! 2 :1): 3/4 (0.17 g, 92%). Colorless
powder. TLC (silica gel, CH2Cl2/MeOH 4:1): Rf 0.36 (one spot). UV (MeOH): 265 (13400).
N-{8-[2-Deoxy-3,5-di-O-(p-toluoyl)-b-d-erythro-pentofuranosyl]-4,8-dihydro-6-iodo-4-oxoimidazo[1,2-a]-
1,3,5-triazin-2-yl}-2-methylpropanamide (9) and N-{8-[2-Deoxy-3,5-di-O-(p-toluoyl)-a-d-erythro-pentofurano-
syl]-4,8-dihydro-6-iodo-4-oxoimidazo[1,2-a]-1,3,5-triazin-2-yl}-2-methylpropanamide (10). The mixture 9/10
(2.1 g, 3.00 mmol) was dissolved in hot MeOH (15 ml). Cooling in the refrigerator (88) for 2 h and filtration gave
the b-d-anomer 9 (0.65 g, 31%) as colorless crystals. The mother liquid was evaporated and redissolved in hot
AcOEt (7 ml); petroleum ether (14ml) was added. The soln. was put in the refrigerator for 2 days. Then the
precipitate was filtered to furnish the a-d-anomer 10 (0.57 g, 27%) as a yellowish solid.
Data of 9: M.p. 160 1618. TLC (silica gel, CH2Cl2/MeOH 200 :1): Rf 0.23. UV (MeOH): 242 (38800).
1H-NMR ((D6)DMSO): 1.01, 1.04(2 s, 2Me); 2.36, 2.39 (2s, 2Me); 2.63 (m, CH), 2.96, 2.99 (2m, 2 HÀC(2')); 4.47
(m, HÀC(4'), 2 HÀC(5')); 5.65 (t, J ˆ 2.93, HÀC(3')); 6.25 (t, J ˆ 6.80 Hz, HÀC(1')); 7.22, 7.76 (2m, HÀC(7), 8
arom. H); 10.28 (s, NH). Anal. calc. for C30H30IN5O7 (699.49): C 51.51, H 4.32, I 18.14, N 10.01; found: C 51.65,
H 4.28, I 18.30, N 10.08.
Data of 10: M.p. 144 1468. TLC (silica gel, CH2Cl2/MeOH 200 :1): Rf 0.23. UV (MeOH): 240 (37700).
1H-NMR ((D6)DMSO): 1.01, 1.04(2 s, 2 Me); 2.32, 2.34(2 s, 2 Me); 2.91 (m, CH, 2 HÀC(2')); 4.47 (d, J ˆ 4.13,
2 HÀC(5')); 4.78 (t, J ˆ 4.13 Hz, HÀC(4')); 5.60 (d, J ˆ 5.02, HÀC(3')); 6.41 (dd, J ˆ 5.73, 1.97, HÀC(1')); 7.17,
7.61, 7.86 (3m, HÀC(7), 8 arom. H); 8.04( s, NH). Anal. calc. for C30H30IN5O7 (699.49): C 51.51, H 4.32, I 18.14,
N 10.01; found: C 51.55, H 4.41, I 18.20, N 10.10.
2-Amino-8-(2-deoxy-b-d-erythro-pentofuranosyl)-6-iodoimidazo[1,2-a]-1,3,5-triazin-4-(8H)-one (3).
Compound 9 (236 mg, 0.34mmol) suspended in NH 3/MeOH (30 ml) was stirred at r.t. overnight. After

Helvetica Chimica Acta Vol. 87 (2004)
2243
evaporation, the residue was purified by FC (silica gel, CH2Cl2/MeOH 15 :1 ! 4:1): 3 (122 mg, 92%). Colorless
powder. TLC (silica gel, CH2Cl2/MeOH 4:1): Rf 0.36. UV (MeOH): 265 (13200). 1H-NMR ((D6)DMSO): 2.13
(d, J ˆ 14.42, 1 HÀC(2')); 2.36 (m, 1 HÀC(2')); 3.51 (m, 2 HÀC(5')); 3.79 (d, J ˆ 2.68, HÀC(4')); 4.29 (s,
HÀC(3')); 4.97 (t, J ˆ 4.86, OHÀC(5')); 5.27 (d, J ˆ 3.33, OHÀC(3')); 6.13 (t, J ˆ 6.71, HÀC(1')); 6.94( s, NH2);
7.57 (s, HÀC(7)). Anal. calc. for C10H12IN5O4 (393.14): C 30.55, H 3.08, I 32.28, N 17.81; found: C 30.65, H 3.15,
I 32.40, N 17.74.
2-Amino-8-(2-deoxy-a-D-erythro-pentofuranosyl)-6-iodoimidazo[1,2-a]-1,3,5-triazin-4-(8H)-one (4). As
described for 3, with 10 (200 mg, 0.29 mmol): 4 (103 mg, 95%). Colorless powder. TLC (silica gel, CH2Cl2/
1
MeOH 4:1): Rf 0.36. UV (MeOH): 265 (12700). H-NMR ((D6)DMSO): 2.09 (d, J ˆ 14.42, 1 HÀC(2')); 2.64
(m, 1 HÀC(2')); 3.39 (m, 2 HÀC(5')); 4.10 (s, HÀC(4')); 4.27 (s, HÀC(3')); 4.83 (t, J ˆ 5.11, OHÀC(5')); 5.49
(d, J ˆ 2.65, OHÀC(3')); 6.14( dd, J ˆ 7.71, 1.92, HÀC(1')); 6.92 (s, NH2); 7.60 (s, HÀC(7)). Anal. calc. for
C10H12IN5O4 (393.14): C 30.55, H 3.08, I 32.28, N 17.81; found: C 30.42, H 3.20, I 32.40, N 17.68.
N-{8-[2-Deoxy-3,5-di-O-(p-toluoyl)-b-l-erythro-pentofuranosyl]-4,8-dihydro-6-iodo-4-oxoimidazo[1,2-a]-
1,3,5-triazin-2-yl}-2-methylpropanamide (11) and N-{8-[2-Deoxy-3,5-di-O-(p-toluoyl)-a-l-erythro-pentofurano-
syl]-4,8-dihydro-6-iodo-4-oxoimidazo[1,2-a]-1,3,5-triazin-2-yl}-2-methylporpanamide (12). As described for 9
and 10, with 8 (0.41 g, 1.18 mmol) and 2-deoxy-3,5-di-O-toluoyl-a-l-erythro-pentofuranosyl chloride (0.7 g,
1.80 mmol): 11 (0.32 g, 39%) and 12 (0.27 g, 33%).
Data of 11: Colorless solid. M.p. 163 1648. TLC (silica gel, CH2Cl2/MeOH 200 :1): Rf 0.23. UV (MeOH):
242 (38600). 1H-NMR ((D6)DMSO): 1.01, 1.04(2 s, 2 Me); 2.37, 2.39 (2s, 2 Me); 2.70 (m, CH); 2.86, 3.08 (2m,
2 HÀC(2')); 4.55 (m, HÀC(4'), 2 HÀC(5')); 5.75 (s, HÀC(3')); 6.34( t, J ˆ 6.69, HÀC(1')); 7.33, 7.86 (2m,
HÀC(7), 8 arom. H); 10.38 (s, NH). Anal. calc. for C30H30IN5O7 (699.49): C 51.51, H 4.32, I 18.14, N 10.01;
found: C 51.57, H 4.10, I 18.30, N 10.10.
Data of 12: Colorless solid. M.p. 139 1408. TLC (silica gel, CH2Cl2/MeOH 200 :1): Rf 0.23. UV (MeOH):
241 (37800). 1H-NMR ((D6)DMSO): 1.01, 1.04(2 s, 2 Me); 2.38 (s, 2 Me); 2.86 (m, CH, 2 HÀC(2')); 4.48 (s, 2
HÀC(5')); 5.10 (s, HÀC(4')); 5.61 (s, HÀC(3')); 6.38 (s, HÀC(1')); 7.33, 7.75, 7.88 (3m, HÀC(7), 8 arom. H);
10.29 (s, NH). Anal. calc. for C30H30IN5O7 (699.49): C 51.51, H 4.32, I 18.14, N 10.01; found: C 51.80, H 4.13,
I 18.29, N 9.95.
2-Amino-8-(2-deoxy-b-l-erythro-pentofuranosyl)-6-iodoimidazo[1,2-a]-1,3,5-triazin-4-(8H)-one (5). As
described for 3, with 11 (210 mg, 0.30 mmol): 5 (113 mg, 96%). Colorless powder. TLC (silica gel, CH2Cl2/
MeOH 4:1): Rf 0.36. UV (MeOH): 265 (12900). 1H-NMR ((D6)DMSO): 2.13 (m, 1 HÀC(2')); 2.36 (m,
1 HÀC(2')); 3.52 (m, 2 HÀC(5')); 4.09 (d, J ˆ 2.60, HÀC(4')); 4.28 (s, HÀC(3')); 4.96 (t, J ˆ 5.12, OHÀC(5'));
5.27 (d, J ˆ 3.71, OHÀC(3')); 6.13 (t, J ˆ 6.65, HÀC(1')); 6.94( s, NH2); 7.57 (s, HÀC(7)). Anal. calc. for
C10H12IN5O4 (393.14): C 30.55, H 3.08, I 32.28, N 17.81; found: C 30.64, H 3.16, I 32.25, N 17.76.
2-Amino-8-(2-deoxy-a-l-erythro-pentofuranosyl)-6-iodoimidazo[1,2-a]-1,3,5-triazin-4-(8H)-one (6). As
described for 3, with 12 (200 mg, 0.29 mmol): 6 (103 mg, 92%). Colorless powder. TLC (silica gel, CH2Cl2/
MeOH 4:1): Rf 0.36. UV (MeOH): 265 (12700). 1H-NMR ((D6)DMSO): 2.10 (d, J ˆ 7.20, 1 HÀC(2')); 2.64( m,
1 HÀC(2')); 3.39 (m, 2 HÀC(5')); 4.10 (s, HÀC(4')); 4.28 (s, HÀC(3')); 4.85 (t, J ˆ 5.38, OHÀC(5')); 5.50 (d,
J ˆ 1.38, OHÀC(3')); 6.15 (d, J ˆ 6.88, HÀC(1')); 6.91, 6.95 (2s, NH2); 7.60 (s, HÀC(7)). Anal. calc. for
C10H12IN5O4 (393.14): C 30.55, H 3.08, I 32.38, N 17.81; found: C 30.52, H 3.15, I 32.50, N 17.45.
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Received May 4, 2004