cis-â-2a: 1H NMR δ ) 3.61 (dd, J ) 10.3, 5.1 Hz, 1 H, H-5A),
3.64 (dd, J ) 10.3, 5.1 Hz, 1 H, H-5B), 4.03 (m, 1 H, H-3), 4.13
(s, 1 H, H-2), 4.40 (q, J ) 5.1 Hz, 1 H, H-4), 4.50 (s, 2 H, PhCH2),
4.54 (d, J ) 11.6 Hz, 1 H, PhCH2), 4.57 (s, 2 H, PhCH2), 4.63 (d,
J ) 11.6 Hz, 1 H, PhCH2), 6.35 and 6.36 (s + dd, J ) 11.4, 7.3
Hz, 2 H, H-1 and H-2′), 6.59 (d, J ) 11.4, 1 H, H-3′), 7.23-7.38
(m, 15 H, 3 x Ph), 10.53 (d, J ) 7.3 Hz, 1 H, H-1′); 13C NMR δ
) 69.5 (t, C-5), 72.10 (t, PhCH2), 72.2 (t, PhCH2), 73.4 (t, PhCH2),
83.3 (d, C-3), 84.2 (d, C-4), 86.7 (d, C-2), 101.5 (d, C-1), 127.8,
127.9, 128.1, 128.3, 128.4 and 128.5 (d, CH of Ph), 133.0 (d, C-3′),
137.0, 137.3, 137.8 (s, Cq of Ph), 141.0 (d, C-2′), 163.1 (s, CO2),
192.2 (d, C-1′).
SCHEME 5
trans-â-4a: 1H NMR (CDCl3) δ ) 3.62 (m, 1 H, H-5A and
5B), 4.00 (d, J ) 5.1 Hz, H-3), 4.11 (s, 1 H, H-2), 4.40 (q, J ) 5.1
Hz, 1 H, H-4), 4.49 (s, 2 H, CH of Ph), 4.52 (d, J ) 12.2 Hz, 1 H,
CH of Ph), 4.54 (s, 2 H, PhCH2), 4.63 (d, J ) 12.2 Hz, 1 H, CH
of Ph), 6.35 (s, 1 H, H-1), 6.68 (d, J ) 16.5 Hz, 1 H, H-3′), 6.97
(dd, J ) 16.5, 7.2 Hz, 1 H, H-2′), 7.20-7.40 (m, 15 H, 3 x Ph),
9.76 (d, J ) 7.2 Hz, H-1′); 13C NMR (CDCl3) δ ) 69.5 (t, C-5),
72.1 (t, PhCH2), 72.2 (t, PhCH2), 73.4 (t, PhCH2), 83.4 (d, C-3),
84.1 (d, C-4), 86.7 (d, C-2), 101.6 (d, C-1), 127.7, 127.8, 127.9,
128.1, 128.3, 128.4, 128.5 (d, CH of Ph), 137.0, 137.4, and 137.8
(s, Cq of Ph), 138.6 (d, C-3′), 141.0 (d, C-2′), 163.8 (s, CO2), 192.1
(d, C-1′).
One-Pot Synthesis of 7c. A 0.02 M solution of 1c (1 mmol)
in dry MeOH was photooxygenated as reported in the general
procedure. When the reaction was complete (30 min), 1.2 equiv
of Et2S was added to the crude methanol solution, and the
resulting mixture was kept at rt under stirring for 60 min. Then,
1.2 equiv of hydrazine hydrochloride was added. After 3 days,
the solvent was removed under reduced pressure, and the
residue, dissolved in ethyl acetate, was extracted with a HCl
solution 1 M (3 × 30 mL). The aqueous solution was neutralized
with a NaOH solution until a basic condition was achieved and
extracted with ethyl acetate (3 × 30 mL). The organic layer was
washed with brine, dried with MgSO4, and filtered. Silica gel
chromatography (CHCl3/MeOH 95:5 v/v) afforded the pyridazine
C-nucleoside â-7c: yield 70%; oil; 1H NMR18 δ ) 2.10 (s, 3 H,
CH3CO), 2.11 (s, 3 H, CH3CO), 2.14 (s, 3 H, CH3CO), 2.67 (s, 3
H, Me-3′), 2.69 (s, 3 H, Me-6′), 4.36 (m, 2 H, H-4 and H-5A), 4.45
(dd, J ) 9.8, 3.8 Hz, 1 H, H-5B), 5.11 (m, 2 H, H-1 and H-2),
5.25 (t, J ) 5.2 Hz, 1 H, H-3), 7.41 (s, 1 H, H-5′); 13C NMR δ )
19.7 (q, Me-3′), 20.4 (q, CH3CO), 20.5 (q, CH3CO), 20.8 (q, CH3-
CO), 22.1 (q, Me-6′), 63.0 (t, C-5), 70.8 (d, C-3), 75.7 (d, C-2),
77.6 (d, C-1), 79.7 (d, C-4), 123.0 (d, C-5′), 136.5 (s, C-4′), 155.2
(s, C-3′), 158.7 (s, C-6′), 169.2 (s, CO2), 167.6 (s, CO2), 170.4 (s,
CO2).
furans. The results confirm both the high diastereo-
selectivity of the reaction, affording only the cis-unsatur-
ated aglycones, and the stereospecificity of the sugar
moiety migration in obtaining O-glycosides. Moreover, a
simple one-pot procedure for a new pyridazine C-nucleo-
side is reported. Compound 7c is structurally related to
pharmacologically active analogues,17 and only a few
synthetic approaches to this compound class are reported
in the literature. Hence, this work demonstrates the use
of dye-sensitized photooxygenation of a glycosyl furan
moiety as an additional methodology in the field of
glycoside organic synthesis. Work is under progress to
extend the procedure to a variety of C-nucleoside deriva-
tives.
Experimental Section
The 1H and 13C NMR spectra, DEPT experiments, 1H-1H
COSY experiments, and heteronuclear chemical shift correla-
tions (HMQC and HMBC pulse sequences) were run on a 500
NMR spectrometer in CDCl3.
General Procedure of Dye-Sensitized Photooxygen-
ation. A 0.02 M solution of 1 (0.25 mmol) in dry CH2Cl2 was
irradiated at -20 °C with a halogen lamp (650 W) in the
presence of methylene blue (MB, 1 × 10-3 mmol), while dry
oxygen was bubbled through the solution. The progress of each
reaction was checked by periodically monitoring (TLC, or 1H
NMR) the disappearance of 1. When the reactions were complete
(ca. 60-90 min), the solutions were heated to rt (entry a) or 40
°C (entry b). Then, after removal of the solvent, each residue
was taken up in Et2O; the suspension was filtered to remove
the insoluble sensitizer (MB), and the filtrate was evaporated
to give cis-2 (yields > 90%). The addition of silica gel to the crude
photooxygenated mixtures and, after 60 min, the removal of
silica gel and MB by filtration afforded trans compound 4 in ca.
70% yields.
Acknowledgment. Financial support from MIUR
(FIRB 2003-2005) is gratefully acknowledged. NMR
experiments were run at the Centro di Metodologie
Chimico-Fisiche, Universita` di Napoli Federico II.
Supporting Information Available: General procedures,
1
spectral and/or physical data for new compounds, H and 13C
NMR spectra, DEPT experiments, 1H-1H COSY experiments,
and heteronuclear chemical shift correlations by HMQC and
HMBC pulse sequences for the pyridazine 7c, together with
mass spectra (EI) of compounds 1c, 5c, and 7c. This material
JO0504159
(17) (a) Borowski, P.; Lang, M.; Haag, A.; Schmitz, H.; Choe, J.;
Chen, H.-M.; Hosmane, R. S. Antimicrob. Agents Chemother. 2002, 46,
1231. (b) Cook, P. D.; Dea, P.; Robins, R. K. J. Heterocycl. Chem. 1978,
15, 1. (c) Joshi, U.; Josse, S.; Pipelier, M.; Chevallier, F.; Pradere, J.-
P.; Hazard, R.; Legoupy, S.; Huet, F.; Dubreuil, D. Tetrahedron Lett.
2004, 45, 1031.
(18) 1H NMR signals of the pyridazine 7c undergo large shifts when
the concentration of the CDCl3 solution is changed. This is probably
due to strong nonbonded intermolecular interactions between one of
the heterocyclic nitrogens with the sufficiently acidic hydrogen at C5′
(δ ) 7.41 ppm).
J. Org. Chem, Vol. 70, No. 16, 2005 6505