Synthesis of new 3'-deoxyribonucleosides employing the acid-catalyzed fusion method

Article abstract of DOI:10.1002/(SICI)1522-2675(19981216)81:12<2326::AID-HLCA2326>3.0.CO;2-4

Coupling of 4,6-dichloro-1H-imidazo[4,5-c]pyridine (2,6-dichloro-3- deaza-9H-purine) (1) with 1,2-O-di-acetyl-5-O-benzoyl-3-deoxy-β-D- ribofuranose (2), employing the acid-catalyzed fusion method, is reported (Scheme 1). The condensation reaction was regi

Full text of DOI:10.1002/(SICI)1522-2675(19981216)81:12<2326::AID-HLCA2326>3.0.CO;2-4

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Helvetica Chimica Acta ± Vol. 81 (1998)
Synthesis of New 3'-Deoxyribonucleosides Employing
the Acid-Catalyzed Fusion Method
by Rosaria Volpini, Emidio Camaioni, Stefano Costanzi, Sauro Vittori, and Gloria Cristalli*
Á
Dipartimento di Scienze Chimiche, Universita di Camerino, I-62032 Camerino
Coupling of 4,6-dichloro-1H-imidazo[4,5-c]pyridine (2,6-dichloro-3-deaza-9H-purine) (1) with 1,2-O-di-
acetyl-5-O-benzoyl-3-deoxy-b-d-ribofuranose (2), employing the acid-catalyzed fusion method, is reported
(Scheme 1). The condensation reaction was regioselective and gave the three N1-glycosylation products 3 ± 5,
whereas no N3-nucleosides were detected. Treatment of 3 ± 5 with methanolic ammonia afforded the
corresponding deprotected nucleosides 6 ± 8. Compounds 6 and 7 were assigned the structure of the b-d- and a-
d-anomeric N1-(3'-deoxyribo)nucleosides, respectively. The third derivative 8 proved to be the a-d-anomer of a
3'-deoxyarabinonucleoside deriving from epimerization at C(2) of the sugar. The 2-chloro- and N6-substituted
derivatives 9, 11, and 13 of 3'-deoxy-3-deazaadenosine (10) and of its a-d-anomer 12 can be obtained from these
versatile synthons (Schemes 2 and 3).
Introduction. ± 3-Deazaadenosine (c3A, I) is an adenosine analogue endowed with
a number of biological effects, probably mediated via interaction with multiple cellular
targets. In the past, it has been shown that this nucleoside weakly interacts with A1
adenosine receptors [1] and adenosine deaminase [2]. On the other hand, it is well-
known that c3A (I) is both an inhibitor and a substrate for S-adenosylhomocysteine
hydrolase (AdoHcyase) [3], the enzyme which catalyzes the reversible hydrolysis of
AdoHcy to l-homocysteine and adenosine. According to the fact that AdoHcyase is
the key enzyme in methylation reactions depending on S-adenosylmethionine as the
methyl donor, including those which are required for the maturation of viral mRNA
[4], I has been reported to inhibit the replication of human immunodeficiency virus
type 1 (HIV-1) [5]. In recent years, it was shown that exposure to I is a stimulus that
initiates apoptotic cell death in human leukemia HL-60 cells [6]. Furthermore, c3A
analogues were reported to induce apoptosis in L1210 leukemia cells [7]. On the other
hand, we have found that c3A was inactive in inducing apoptosis in human peripheral
blood mononuclear cells (PBMC), whilst its 2-chloro-2'-deoxy derivative triggered
apoptosis in the same cell line [8].

Helvetica Chimica Acta ± Vol. 81 (1998)
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These findings prompted us to select 3-deazapurine derivatives in an effort to
synthesize deazanucleosides endowed with pharmacological activity. In particular, on
the basis that 3'-deoxyribonucleosides exhibit a number of biological activites, e.g.,
antifungal, antibacterial, antiparasitic, and anticancer activity [9], and a high affinity
for adenotin [10][11], we coupled 2,6-dichloro-3-deazapurine (1) with the 3-deoxy-
ribose derivative 2 to obtain compounds of the general formula II.
Results. ± The 4,6-dichloro-1H-imidazo[4,5-c]pyridine (1) [12] was treated with 1,2-
di-O-diacetyl-5-O-benzoyl-3-deoxy-b-d-ribofuranose (2) [13] in the presence of a
catalytic amount of p-toluenesulfonic acid (TsOH) at 1608 in vacuo for 10 min
(Scheme 1). The coupling gave a mixture of b-d- and a-d-anomeric N1-(3'-deoxyribo)-
nucleosides 3 and 4, respectively, and a third isomer identified as the a-d-anomer 5 of
N1-(3'-deoxyarabino)nucleoside deriving from epimerization at C(2) of the sugar. A
similar epimerization has been reported to occur under fusion reaction conditions in
the case of ribose derivatives [14]. The total yield of nucleosides was 90%.
Scheme 1
The glycosylation site and the anomeric configuration were assigned on the basis of
1
1
UV data and H-NMR spectra, including 1D H-NOE difference spectra, of the
deprotected nucleosides 6 ± 8, obtained by reacting 3 ± 5 with methanolic ammonia
(Scheme 1).
The UV spectra of the three nucleosides 6 ± 8 are essentially identical (see Exper. Part). Furthermore, a
NOE at H C(2) and H C(7) upon saturation of H C(1') establishes N(1) as glycosylation site in all three
cases [15] (see Table). Saturation of H C(1') of compound 6 results in a NOE at the H C(4') (and H C(2'))

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Helvetica Chimica Acta ± Vol. 81 (1998)
signal (6.0%), establishing the b-d-configuration. On the other hand, saturation of H C(1') of compound 7
gives rise to a NOE at the Ha C(3') signal (1.0%), while there is none at H C(4'), establishing the a-d-
configuration. Similarly, irradiation of H C(1') of 8 gives a NOE of 0.9% at the Ha C(3') signal and none at
H
C(4'), establishing the a-d-configuration. Saturation of both H C(2') and H C(4') of 8 produces a NOE at
the Hb C(3') signal (3.1 and 2.9%, resp.), demonstrating that the sugar moiety is a deoxyarabinose derivative.
Table. NOE Data [%] of Imidazo[4,5-c]pyridine Nucleosides in (D6)DMSO at 238
Irradiated proton
Observed NOE [%]
6
7
8
H
H
H
H
H
C(1')
C(1')
C(1')
C(4')
C(2')
H
H
H
H
H
C(2) (9.2), H C(7) (17.8), H C(4') (and H C(2')) (6.0)
C(2) (4.2), H C(7) (6.7), H C(2') (6.8), Ha C(3') (1.0)
C(2) (4.2), H C(7) (6.5), H C(2') (2.0), Ha C(3') (0.9)
C(2) (1.7), H C(7) (1.4), Hb C(3') (2.9)
C(2) (3.0), H C(7) (3.0), H C(1') (2.1), Hb C(3') (3.1)
Treatment of 6 or 7 with hydrazine hydrate gave the corresponding crude hydrazino
intermediates which were refluxed in the presence of Raney-Ni catalyst to afford the 4-
amino-6-chloro-1-(3-deoxy-b-d- and -a-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridines
(9 and 11, resp.), respectively (Scheme 2). Catalytic hydrogenolysis of the Cl-atom in 9
or 11 with 10% Pd/C in abs. EtOH and in the presence of 1n NaOH afforded the target
compound 10 and its anomer 12, respectively. The structure of 10 was confirmed by
comparing its 1H-NMR and UV spectra with those of the same compound synthesized
by Matsuda et al., starting from 3'-deoxyinosine [16].
Compound 6 was also treated with cyclohexylamine, at 1058 for 16 h, and the ob-
tained 6-chloro-4-(cyclohexylamino)-1-(3-deoxy-b-d-ribofuranosyl)-1H-imidazo[4,5-
c]pyridine (13) was dechlorinated using the above mentioned conditions to give 14
(Scheme 3).
Scheme 2

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2329
Scheme 3
Experimental Part
1. General. M.p.: Büchi apparatus, uncorrected. UV Spectra: Perkin-Elmer-Coleman-575 spectrophotom-
eter. 1H-NMR Spectra: Varian-VXR-300 spectrometer; d in ppm, J in Hz. TLC: TLC plates precoated with silica
gel 60 F-254 (Merck). Flash chromatography (FC): silica gel 60 (Merck). Elemental analyses: Carlo-Erba-1106
analyser, exper. values within Æ0.4% of calc. values.
2. Glycosylation of 1 with 2. An intimate mixture of 4,6-dichloro-1H-imidazo[4,5-c]pyridine (1) [12]
(250 mg, 1.33 mmol), 1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-b-d-ribofuranose (2) [13] (857 mg, 2.66 mmol) and
TsOH (cat. amount) was heated at 1608. When the fusion started, vacuum from a water aspirator (25 Torr) was
applied until bubbling ceased (5 ± 10 min). The resulting solid was submitted to FC (silica gel, cyclohexane/
AcOEt 7:3): mixture 3 ± 5 (540 mg, 90%). Anal. samples of 3, 4, and 5 were obtained by prep. TLC (CHCl3/
MeOH 98:2).
1-(2-O-Acetyl-5-O-benzoyl-3-deoxy-b-d-ribofuranosyl)-4,6-dichloro-1H-imidazo[4,5-c]pyridine (3): Yield
52%. Rf 0.62. UV (EtOH): 259(8600), 273(7500). 1H-NMR ((D6)DMSO): 1.98 ± 2.10 (m, 1 H C(3'));
2.15 (s, MeCO); 2.24 ± 2.38 (m, 1 H C(3')); 4.45 ± 4.80 (m, 2 H C(5'), H C(4')); 5.59 (d, J ˆ 6.1, H C(2'));
6.36 (s, H C(1')); 7.48 ± 7.56 (m, 2 arom. H); 7.65 ± 7.74 (m, 1 arom. H); 7.86 ± 7.94 (m, 2 arom. H); 7.95
(s, H C(7)); 8.72 (s, H C(2)). Anal. calc. for C20H17Cl2N3O5 (450.28): C 53.35, H 3.81, N 9.33; found: C 53.55,
H 4.03, N 9.07.
1-(2-O-Acetyl-5-O-benzoyl-3-deoxy-a-d-ribofuranosyl)-4,6-dichloro-1H-imidazo[4,5-c]pyridine (4): Yield
24%. Rf 0.52. UV (EtOH): 259(8500), 273(7400). 1H-NMR ((D6)DMSO): 1.72 (s, MeCO); 2.42 ± 2.58 (m, 2
H
H
C(3')); 4.38 ± 4.62 (m, 2
H
C(5')); 5.01 ± 5.15 (m, H C(4')); 5.59 ± 5.70 (m, H C(2')); 6.67 (d, J ˆ 4.0,
C(1')); 7.59 ± 7.78 (m, 3 arom. H); 7.94 (s, H C(7)); 8.03 ± 8.10 (m, 2 arom. H); 8.71 (s, H C(2)). Anal.
calc. for C20H17Cl2N3O5 (450.28): C 53.35, H 3.81, N 9.33; found: C 53.47, N 3.93, N 9.15.
1-(2-O-Acetyl-5-O-benzyl-3-deoxy-a-d-arabinofuranosyl)-4,6-dichloro-1H-imidazo[4,5-c]pyridine (5): Yield
14%. Rf 0.57. UV (EtOH): 259(8600), 273(7500). 1H-NMR ((D6)DMSO): 2.04 (s, MeCO); 2.05 ± 2.14 (m, 2
H
C(3')); 4.21 ± 4.35 (m, 2 H C(5')); 4.91 ± 4.93 (m, H C(4')); 5.18 ± 5.20 (m, H C(2')); 6.71 (s, H C(1'));
7.61 ± 7.78 (m, 3 arom. H); 7.94 (s, H C(7)); 8.03 ± 8.10 (m, 2 arom. H); 8.71 (s, H C(2)). Anal. calc. for
C20H17Cl2N3O5 (450.28): C 53.35, H 3.81, N 9.33; found: C 53.45, H 3.90, N 9.17.
3. 4,6-Dichloro-1-(3-deoxy-b-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (6), 4,6-Dichloro-1-(3-deoxy-a-
d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (7), and 4,6-Dichloro-1-(3-deoxy-a-d-arabinofuranosyl)-1H-imi-
dazo[4,5-c]pyridine (8). To the mixture 3 ± 5 (540 mg, 1.2 mmol), MeOH saturated at 08 with ammonia (40 ml)
was added, and the mixture was allowed to stand at r.t. for 24 h. After evaporation, the residue was separated by
FC (CHCl3/MeOH 96:4): 6 (187 mg, 51%), 7 (82 mg, 23%), and 8 (45 mg, 13%) as amorphous solids.
Data of 6: Rf 0.18. UV (EtOH): 259(13400). 1H-NMR ((D6)DMSO): 1.81 ± 1.97 (m, 1 H C(3')); 2.01 ±
2.19 (m, 1 H C(3')); 3.50±3.65 (m, 1 H C(5')); 3.72±3.88 (m, 1 H C(5')); 4.36±4.52 (m, H C(2'), H C(4'));
5.96 (s, H C(1')); 8.07 (s, H C(7)); 8.84 (s, H C(2)). Anal. calc. for C11H11Cl2N3O3 (304.13): C 43.44, H 3.65,
N 13.82; found: C 43.58, H 3.77, N 13.65.
1
Data of 7: Rf 0.10. UV (EtOH): 259(13100). H-NMR ((D6)DMSO): 1.94 ± 2.23 (m, 2 H C(3')); 3.38 ±
3.65 (m, 2 H C(5')); 4.48 ± 4.59 (m, H C(2')); 4.60 ± 4.70 (m, H C(4')); 6.29 (d, J ˆ 4.1, H C(1')); 7.89 (s,
H
C(7)); 8.56 (s, H C(2)). Anal. calc. for C11H11Cl2N3O3 (304.13): C 43.44, H 3.65, N 13.82; found: C 43.57,
H 3.72, H 13.60.

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Helvetica Chimica Acta ± Vol. 81 (1998)
Data of 8: Rf 0.23. UV (EtOH): 259(13600). 1H-NMR ((D6)DMSO): 1.79 ± 1.86 (m, 1 H C(3')); 2.25 ±
2.42 (m, 1 H C(3')); 3.45 ± 3.60 (m, 2 H C(5')); 4.47 ± 4.58 (m, H C(4')); 4.58 ± 4.70 (m, H C(2')); 5.96 (d,
J ˆ 3.9, H C(1')); 7.96 (s, H C(7)); 8.70 (s, H C(2)). Anal. calc. for C11H11Cl2N3O3 (304.13): C 43.44, H 3.65,
N 13.82; found: C 43.60, H 3.73, N 13.63.
4. 4-Amino-6-chloro-1-(3-deoxy-b-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (9) and 4-Amino-6-chloro-
1-(3-deoxy-a-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (11). Compound 6 or 7 (82 mg, 0.27 mmol) was
stirred at r.t. for 5 h in the presence of hydrazine hydrate (5 ml). After evaporation, the hydrazino intermediate,
Raney-Ni catalyst (200 mg), and O2-free H2O (10 ml) were refluxed for 1 h. The mixture was filtered, the filtrate
evaporated, and the residue crystallized from MeCN: 9 (31 mg, 41%) or 11 (35 mg, 46%), resp., as
chromatographically pure solids.
Data of 9: M.p. 122 ± 1258. UV (EtOH): 272(13800). 1H-NMR ((D6)DMSO): 1.79 ± 1.98 (m, 1 H C(3'));
2.07 ± 2.25 (m, 1 H C3')); 3.49 ± 3.63 (m, 1 H C(5')); 3.67 ± 3.82 (m, 1 H C(5')); 4.30 ± 4.48 (m, H C(2'),
H
C(4')); 5.74 (s, H C(1')); 6.72 (s, NH2); 6.99 (s, H C(7)); 8.37 (s, H C(2)). 13C-NMR ((D6)DMSO):
32.91 (C(3')); 61.75 (C(5')); 74.67 (C(2')); 80.62 (C(4')); 91.88 (C(1')); 95.26 (C(7)); 125.60 (C(3a));
138.86 (C(7a)); 139.96 (C(2)); 141.03 (C(6)); 151.27 (C(4)). Anal. calc. for C11H13ClN4O3 (284.70): C 46.41,
H 4.60, N 19.68; found: C 46.61, H 4.73, N 19.48.
Data of 11: M.p. 142 ± 1448. UV (EtOH): 272(13600). 1H-NMR ((D6)DMSO): 1.94 ± 2.20 (m, 2 H C(3'));
3.38 ± 3.61 (m, 2
H
C(5')); 4.41 ± 4.59 (m, H C(2'),
H
C(4')); 6.08 (d, J ˆ 4.0,
H C(1')); 6.65 (s, NH2);
6.87 (s, H C(7)); 8.11 (s, H C(2)). 13C-NMR ((D6)DMSO): 34.53 (C(3')); 63.22 (C(5')); 70.53 (C(2'));
79.02 (C(4')); 87.45 (C(1')); 95.82 (C(7)); 125.07 (C(3a)); 139.78 (C(7a)); 140.67 (C(6)); 141.26 (C(2));
151.09 (C(4)). Anal. calc. for C11H13ClN4O3 (284.70): C 46.41, H 4.60, N 19.68; found: C 46.65, H 4.70, N 19.51.
5. 4-Amino-1-(3-deoxy-b-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (10) and 4-Amino-1-(3-deoxy-a-d-
ribofuranosyl)-1H-imidazo[4,5-c]pyridine (12). To 9 or 11 (30 mg, 0.1 mmol) in abs. EtOH (10 ml), 1n NaOH
(1 ml) and a cat. amount of 10% Pd/C were added. The mixture was hydrogenated under 40 psi for 6 h. The
catalyst was removed by filtration and the filtrate evaporated. Purification by prep. TLC (CHCl3/MeOH 7:3)
gave 10 (24 mg, 87%) or 12 (18 mg, 65%), resp., as colorless solids.
Data of 10: M.p. 2378 ([16]: 220 ± 2228). UV (H2O): 262(9800): 1H-NMR ((D6)DMSO): 1.80 ± 1.98
(m, Hb C(3')); 2.08 ± 2.27 (m, Ha C(3')); 3.47 ± 3.62 (m, 1 H C(5')); 3.63 ± 3.78 (m, 1 H C(5')); 4.29 ± 4.46
(m, H C(4'), H C(2')); 5.78 (s, H C(1')); 6.18 (s, NH2); 6.90 (d, J ˆ 5.9, H C(7)); 7.69 (d, J ˆ 5.9, H C(6));
8.35 (s, H C(2)). Anal. calc. for C11H14N4O3 (250.26): C 52.79, H 5.64, N 22.39; found: C 52.91, H 5.72, N 22.17.
Data of 12: M.p. 2308 (dec.). UV (H2O): 262(10200). 1H-NMR ((D6)DMSO): 1.98 ± 2.23 (m, 2 H C(3'));
3.35 ± 3.63 (m, 2
H
C(5')); 4.43 ± 4.58 (m, H C(4'),
H
C(2')); 6.10 (d, J ˆ 4.1,
H C(1')); 6.14 (s, NH2);
6.82 (d, J ˆ 5.9, H C(7)); 7.66 (d, J ˆ 5.9, H C(6)); 8.10 (s, H C(2)). Anal. calc. for C11H14N4O3 (250.26):
C 52.79, H 5.64, N 22.39; found: C 52.88, H 5.73, N 22.19.
6. 6-Chloro-4-(cyclohexylamino)-1-(3-deoxy-b-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (13). To
6
(162 mg, 0.53 mmol), cyclohexylamine (10 ml) was added, and the mixture was heated at 1058 for 16 h. The
exceeding amine was evaporated and the residue purified by FC (CHCl3/MeOH 98:2) to give a colorless solid
1
which was crystallized from MeCN: 13 (150 mg, 75%). M.p. 1308 (dec.). UV (EtOH): 282(16700). H-NMR
((D6)DMSO): 0.85±1.99 (m, 10 cyclohexyl H, 1 H C(3')); 2.04±2.23 (m, 1 H C(3')); 3.50±3.62 (m, 1 H C(5'));
3.68 ± 3.82 (m, 1 H C(5')); 3.89 ± 4.12 (m, 1 cyclohexyl H); 4.30 ± 4.45 (m, H C(2'), H C(4')); 5.75 (d, J ˆ 2.0,
H
C(1')); 6.83 (d, J ˆ 8.6, NH); 6.95 (s, H C(7)); 8.37 (s, H C(2)). Anal. calc. for C17H23ClN4O3 (366.85):
C 55.66, H 6.32, N 15.27; found: C 55.80, H 6.47, N 15.14.
7. 4-(Cyclohexylamino)-1-(3-deoxy-b-d-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (14). As described in
Exper. 5, with 13 (70 mg, 0.19 mmol), abs. EtOH (15 ml), 1n NaOH (2 ml), and a cat. amount of 10% Pd/C.
Purification by FC (CHCl3/MeOH 92:8) gave a colorless solid which was crystallized from MeCN: 14 (35 mg,
58%). M.p. 2008 (dec.). UV (EtOH): 275(14800). 1H-NMR ((D6) DMSO): 1.10 ± 2.04 (m, 10 cyclohexyl H,
1 H C(3')); 2.06 ± 2.27 (m, 1 H C(3')); 3.48 ± 3.62 (m, 1 H C(5')); 3.64 ± 3.78 (m, 1 H C(5')); 3.93 ± 4.27
(m, 1 cyclohexyl H); 4.30 ± 4.45 (m, H C(2'), H C(4')); 5.77 (d, J ˆ 2.1, H C(1')); 6.19 (d, J ˆ 8.5, NH);
6.86 (d, J ˆ 5.8, H C(7)); 7.75 (d, J ˆ 5.8, H C(6)); 8.33 (s, H C(2)). Anal. calc. for C17H24N4O3 (332.40):
C 61.43, H 7.28, N 16.86; found: C 61.63, H 7.41, N 16.60.
REFERENCES
[1] G. Cristalli, M. Grifantini, S. Vittori, W. Balduini, F. Cattabeni, Nucleosides Nucleotides 1985, 4, 625.
[2] G. Lupidi, G. Cristalli, F. Marmocchi, F. Riva, M. Grifantini, J. Enzyme Inhib. 1985, 1, 67.
[3] P. K. Chiang, R. M. Smejkal, Rev. Biol. Cell. 1987, S1, 41.

Helvetica Chimica Acta ± Vol. 81 (1998)
[4] E. DeClerq, Nucleosides Nucleotides 1998, 17, 625.
2331
[5] D. L. Mayers, J. A. Mikovits, H. Bharat, I. K. Hewlett, J. S. Estrada, A. D. Wolfe, G. E. Garcia, B. P. Doctor,
D. S. Burke, R. K. Gordon, J. R. Lane, P. K. Chiang, Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 215.
[6] P. C. Endresen, T. J. Eide, J. Aarbakke, Biochem. Pharmacol. 1993, 46, 1893.
[7] I.-K. Kim, C.-C. H. Li, H. A. Young, J.-H. Lee, H.-S. Kim, K. Pardhasaradhi, G. E. Garcia, P. K. Chiang, J.
Biomed. Sci. 1997, 4, 83.
[8] D. Barbieri, C. Franceschi, E. Camaioni, S. Costanzi, S. Vittori, R. Volpini, G. Cristalli, Biorg. Med. Chem.
Lett. 1998, 8, 2533.
[9] A. Kumar, S. I. Khan, A. Manglani, Z. K. Khan, S. B. Katti, Nucleosides Nucleotides 1994, 13, 1049.
[10] R. Volpini, E. Camaioni, E. Di Francesco, S. Vittori, T. Fein, U. Schwabe, G. Cristalli, Collect. Czech. Chem.
Commun. 1996, 61, S33.
[11] R. Volpini, E. Camaioni, S. Vittori, L. Barboni, C. Lambertucci, G. Cristalli, Helv. Chim. Acta 1998, 81, 145.
[12] R. J. Rousseau, R. K. Robins, J. Heterocycl. Chem. 1965, 2, 196.
[13] C. J. Rizzo, J. P. Dougherty, R. Breslow, Tetrahedron Lett. 1992, 33, 4129.
[14] J. J. Fox, K. A. Watanabe, Tetrahedron Lett. 1966, 7, 896; P. C. Srivastava, R. K. Robins, R. B. Mayer,
ꢀSynthesis and Properties of Purine Nucleosides and Nucleotidesꢁ, in ꢀChemistry of Nucleosides and
Nucleotidesꢁ, Ed. L. B. Townsend, Plenum Press, New York, 1988, Vol. 1, pp. 135, 136.
[15] H. Rosenmeyer, G. Toth, F. Seela, Nucleosides Nucleotides 1989, 8, 587.
[16] N. Minakawa, Y. Sasabuchi, A. Kiyosue, N. Kojima, A. Matsuda, Chem. Pharm. Bull. 1996, 44, 288.
Received June 19, 1998