2624
Z. Han et al. / Tetrahedron 64 (2008) 2619e2625
3.95 (t, J¼6.9 Hz, 2H, 10-H), 4.15 (s, 3H, N7eCH3). 13C:
d (CDCl3) 20.9 (C-20), 27.4 (C-30), 29.4 and 29.6 (C-200 and
C-300), 29.9 (C-60), 31.4 (N3eC), 34.0 (N7eC), 40.7 (C-10),
43.2 (C-40), 70.8 (C-100), 108.5 (C-5), 146.7 (C-8), 151.4
(C-4), 155.3 (C-2), 157.0 (C-6), 208.9 (C-50). The fractions
with Rf 0.32, 0.26 and 0.14 correspond to products 4, 5 and 6.
benzophenone at a concentration of 0.05 mmol/L, tributyltin
hydride (600 mL/50 mL), di-tert-butyl peroxide (DTBP) in
a catalytic amount (2 mL/50 mL) and atmospheric air was
bubbled through the reaction mixture to provide oxygen).
The solvent was flushed with nitrogen and irradiated under ni-
trogen (unless oxygen was used in which case air was bubbled
through) for 24 h. The solvent was removed under reduced
pressure and the product purified by TLC (hexane/ethylace-
tate/acetone/methanol; 2:7:0.5:0.5). Yields are noted in Table 1.
5.3.3. 8-(1-Hydroxymethyl)-3,7-dimethyl-1-(5-oxohexyl)-3,7-
dihydro-1H-purine-2,6-dione 8
Pentoxifylline (278 mg, 1 mmol) was dissolved in metha-
nol (100 mL). The solution was flushed with nitrogen and irra-
diated for 24 h at 300 nm under nitrogen. The solvent was
removed under vacuum. TLC (hexane/ethylacetate/acetone/
methanol; 2:7:0.5:0.5) yielded compound 8, Rf 0.18 (62 mg,
48%), as white needles from chloroform, mp: 177e178 ꢂC.
Found Mþ 308.14830, C15H22N4O4 requires Mþ 308.14846,
Mþ 308 (27), m/e 290 (18), 247 (13), 233 (100), 219 (18),
206 (8.7), 193 (27.2), 180 (67.5), 137 (7.5), 109 (26.4), 82
(14.7), 67 (11.1). IR: nmax 3245, 1703, 1655, 1442, 1033,
Acknowledgements
Financial support from the University of the Free State, Tech-
nology and Human Resources for Industry Program (THRIP),
and FARMOVS-PAREXEL is gratefully acknowledged.
We also acknowledge Dr. Hans Hundt for assistance with
HPLC and Professor Rui de Carvalho (University of Coimbra,
Portugal) for assistance with NOE/NMR spectra.
1
761, 752 cmꢁ1. H: d (CDCl3) 1.62e1.68 (m, 4H, 20-H and
Supplementary data
30-H), 2.14 (s, 3H, 60-H), 2.50 (t, J¼7.1 Hz, 2H, 40-H), 3.54
13
(s, 3H, N3eCH3), 4.01 (t, J¼7.0 Hz, 2H, 10-H), 4.00 (s,
Supplementary data associated with this article can be
N7eCH3), 4.76 (s, 2H, 100-H). C: d (CDCl3) 20.9 (C-20),
27.4 (C-30), 29.6 (C-60), 29.9 (N3eC), 32.0 (N7eC), 40.8
(C-10), 43.2 (C-40), 56.6 (C-100), 108.3 (C-5), 147.4 (C-8),
151.3 (C-4), 151.5 (C-2), 155.3 (C-6), 208.8 (C-50). The frac-
tions Rf 0.32, 0.26 and 0.14 correspond to products 4, 5 and 6
described above.
References and notes
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5.3.4. 8-(1-Hydroxyethyl)-3,7-dimethyl-1-(5-oxohexyl)-3,7-
dihydro-1H-purine-2,6-dione 9
Pentoxifylline (278 mg, 1 mmol) was dissolved in ethanol
(100 mL). The solution was flushed with nitrogen and irradi-
ated for 24 h at 300 nm under nitrogen. The solvent was re-
moved under vacuum. TLC (hexane/ethylacetate/acetone/
methanol; 2:7:0.5:0.5) yielded compound 9, Rf 0.32 (98 mg,
66%), as white needles from chloroform, mp: 186e187 ꢂC.
Found Mþ 322.16408, C15H22N4O4 requires Mþ 322.16411,
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1
2925, 1700, 1638, 1454, 763, 755 cmꢁ1. H: d (CDCl3) 1.63
(d, J¼6.7 Hz, 3H, 200-H), 1.65 (m, 4H, 20-H and 30-H), 2.14
(s, 3H, 60-H), 2.50 (t, J¼7.1 Hz, 2H, 40-H), 3.52 (s, 3H, N3e
CH3), 4.00 (t, J¼7.2 Hz, 2H, 10-H), 4.00 (s, 3H, N7eCH3),
4.99 (dd, J¼12.6, 6.5 Hz, 2H, 100-H). 13C: d (CDCl3) 20.9
(C-20), 22.1 (C-200), 27.4 (C-30), 29.6 (C-60), 29.9 (N3eC),
32.1 (N7eC), 40.7 (C-10), 43.2 (C-40), 62.9 (C-100), 108.5
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5.4. Sensitisation and solvent influence studies
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5.4.1. Standard procedures
Pentoxifylline (278 mg, 1 mmol) was dissolved in the sol-
vent (50 mL) as indicated in Table 1. The additive indicated
in Table 1 was added (naphthalene, acetophenone and