reflux, for 30 min. The products were evaporated under reduced
pressure and then fractionated by short-column chromato-
graphy on silica gel; the appropriate fractions, which were
eluted with chloroform–methanol (97:3 v/v) were evaporated
under reduced pressure to give the title compound 10 (1.06 g,
15.8% overall yield for the 7 steps starting from uridine) (Found,
in material crystallised from absolute ethanol: C, 53.5; H, 5.3;
N, 7.3. C17H20N2O6S requires C, 53.67; H, 5.30; N, 7.36%), mp
144–146 ЊC; δH [(CD3)2SO] 3.19 (1 H, dd, J 4.9 and 9.3), 3.63
(1 H, m), 3.72 (3 H, s), 3.73–3.83 (3 H, m), 4.01 (2 H, m), 5.27
(1 H, t, J 4.7), 5.58 (1 H, d, J 8.1), 5.65 (1 H, d, J 1.7), 5.92 (1 H,
d, J 5.2), 6.84 (2 H, d, J 8.6), 7.24 (2 H, d, J 8.6), 8.02 (1 H, d,
J 8.1), 11.29 (1 H, br s); δC [(CD3)2SO] 34.4, 45.3, 55.0, 59.4,
75.5, 84.5, 90.1, 100.9, 113.0, 130.1, 140.2, 150.4, 158.2, 163.2.
(b) A solution of 1-(2Ј,5Ј-di-O-trityl-β--xylofuranosyl)-
uracil)11 15 (3.32 g, 4.5 mmol) and methanesulfonyl chloride
(1.76 cm3, 22.7 mmol) in dry pyridine (18 cm3) was stirred at
room temperature. After 24 h, the products were cooled to 0 ЊC
(ice–water-bath) and saturated aq. sodium hydrogen carbonate
(10 cm3) was added, followed by dichloromethane (300 cm3).
The resulting mixture was extracted, first with saturated aq.
sodium hydrogen carbonate (2 × 200 cm3) and then with water
(200 cm3). The dried (MgSO4) organic layer was evaporated
under reduced pressure and the residue was co-evaporated with
dry toluene (2 × 15 cm3) to give the putative 3Ј-O-mesyl
derivative 16 as a foam.
The above material 12 (0.224 g) and 1-(2-fluorophenyl)-4-
methoxy-1,2,3,6-tetrahydropyridine13 13 (0.71 g, 3.4 mmol)
were dissolved in dry acetonitrile (6 cm3) and the resulting solu-
tion was evaporated under reduced pressure. After this process
had been repeated, the residue was dissolved in dichloro-
methane (9 cm3), and TFA (0.29 cm3, 3.8 mmol) was added.
The reaction solution was stirred at room temperature. After 17
h, triethylamine (1.05 cm3, 7.5 mmol) was added and the prod-
ucts were evaporated under reduced pressure. The residue was
dissolved in chloroform (50 cm3) and the resulting solution was
washed with saturated aq. sodium hydrogen carbonate (2 × 25
cm3). The combined aqueous layers were back-extracted with
chloroform (25 cm3). The combined organic layers were dried
(MgSO4), and evaporated under reduced pressure. The residue
was fractionated by short-column chromatography on silica gel:
the appropriate fractions, which were eluted with chloroform–
methanol (95.5:0.5 to 99:1 v/v), were combined and evapor-
ated under reduced pressure to give the title compound 14
as a yellow foam [0.32 g; ≈70% overall yield for the two steps
based on 3Ј-S-(4-methoxybenzyl)-3Ј-thiouridine 10 as starting
material]; δH [(CD3)2SO] 1.73 (4 H, m), 1.86 (1 H, m), 2.00 (3 H,
m), 2.75–2.95 (6 H, m), 3.05 (3 H, s), 3.15 (5 H, m), 3.51 (1 H,
dd, J 4.1 and 11.0), 3.62 (1 H, m), 3.93 (1 H, m), 4.45 (1 H, m),
4.98 (1 H, t, J 6.0), 5.77 (1 H, d, J 8.1), 6.07 (1 H, d, J 5.3), 6.8–
7.2 (8 H, m), 7.89 (1 H, d, J 8.1), 8.48 (1 H, d, J 9.0), 8.54 (1 H,
dd, J 2.4 and 9.0), 8.82 (1 H, d, J 2.3), 11.49 (1 H, br s);
δC [(CD3)2SO] 32.5, 32.6, 32.8, 33.5, 47.3, 47.4, 47.5, 47.7, 48.0,
52.5, 60.2, 72.9, 79.2, 82.3, 87.2, 98.2, 100.5, 102.5, 140.8, 150.7,
162.9 and signals assignable to the resonances of the 18 aryl
carbon atoms.
4-Methoxytoluene-α-thiol 7 (2.09 cm3, 15 mmol) was added
dropwise to a solution of sodium hydride (60% dispersion in
mineral oil; 0.546 g, 13.65 mmol) in DMA (20 cm3) at 0 ЊC (ice–
water-bath). The cooling bath was then removed. The solution
obtained was stirred at room temperature for 15 min and was
then added to the above 3Ј-O-mesyl derivative 16. The reactants
were heated at 110 ЊC. After 2 h, the products were cooled and
dichloromethane (200 cm3) was added. The resulting solution
was washed with saturated aq. sodium hydrogen carbonate
(2 × 200 cm3). The combined aqueous layers were back-
extracted with dichloromethane (100 cm3). The organic layers
were combined, dried (MgSO4), and evaporated under reduced
pressure. The residue was heated with acetic acid–water (4:1
v/v; 30 cm3), under reflux. After 30 min, the products were
concentrated under reduced pressure and re-evaporated with
cyclohexane (2 × 15 cm3). The residue was fractionated by
short-column chromatography on silica gel: the appropriate
fractions, which were eluted with chloroform–methanol (99:1
to 98:2 v/v), were combined, and evaporated under reduced
pressure to give the title compound 10 (0.265 g, 15.3% overall
yield for the 3 steps), identical (1H, 13C NMR) to the material
obtained in (a) above.
Triethylammonium salt of 3-N-benzoyl-2Ј,3Ј-di-O-benzoyl-
uridine 5Ј-H-phosphonate 18
Uridine 4 (5.00 g, 20.5 mmol), chlorotriphenylmethane (6.29 g,
22.6 mmol) and pyridine (60 cm3) were stirred together in an
atmosphere of argon at 100 ЊC. After 1.5 h, the products were
cooled to 0 ЊC (ice–water-bath) and benzoyl chloride (21.43
cm3, 0.184 mol) was added. The reactants were then allowed to
warm up to room temperature. After 14 h, the stirred products
were cooled to 0 ЊC and water (20 cm3) was added slowly.
After a further period of 10 min, solid sodium hydrogen
carbonate (20 g) was added very carefully in portions. After 15
min, the products were concentrated under reduced pressure
and the residue was partitioned between chloroform (400 cm3)
and saturated aq. sodium hydrogen carbonate (300 cm3). The
solid precipitate was removed by filtration and the layers were
separated. The organic layer was back-extracted with chloro-
form (2 × 150 cm3). The combined organic layers were dried
(MgSO4), and evaporated under reduced pressure. After the
residue had been coevaporated with toluene under reduced
pressure, it was dissolved in acetic acid–water (4:1 v/v; 75 cm3)
and the solution was heated under reflux. After 1.5 h, the
products were concentrated under reduced pressure and the
residue was coevaporated with cyclohexane (2 × 50 cm3). The
residual material was fractionated by short-column chromato-
graphy on silica gel: the appropriate fractions, which were
eluted with chloroform–methanol (99:1 v/v), were combined,
and evaporated under reduced pressure. Crystallisation of the
residual glass from absolute ethanol gave 3-N-benzoyl-2Ј,3Ј-di-
O-benzoyluridine 17 as colourless needles (5.51 g, 48.3%), mp
191–193 ЊC (lit.14 191–193 ЊC); δH [(CD3)2SO] 3.83 (2 H, m),
4.53 (1 H, m), 5.63 (1 H, m), 5.79 (2 H, m), 6.12 (1 H, d, J 8.2),
6.30 (2 H, d, J 5.3), 7.40 (2 H, m), 7.45–7.7 (6 H, m), 7.77 (3 H,
m), 7.79 (4 H, m), 8.31 (1 H, d, J 8.2).
3Ј-S-(2,4-Dinitrophenylsulfanyl)-2Ј,5Ј-bis-O-[1-(2-fluorophenyl)-
4-methoxypiperidin-4-yl]-3Ј-thiouridine 14
TFA (0.115 cm3, 1.5 mmol) was added to a stirred solution
of 3Ј-S-(4-methoxybenzyl)-3Ј-thiouridine 10 (0.190 g, 0.5
mmol) and 2,4-dinitrobenzenesulfenyl chloride 11 (0.234 g, 1.0
mmol) in dry dichloromethane (8 cm3) at 0 ЊC (ice–water-bath).
After 15 min, the products were evaporated under reduced pres-
sure. A solution of the residue in chloroform–methanol (95:5
v/v; 10 cm3) was pre-adsorbed on silica gel (3 g). The products
were then fractionated by short-column chromatography on
silica gel: elution of the column with chloroform–methanol
(97:3 v/v) and concentration of the appropriate fractions gave
3Ј-S-(2,4-dinitrophenylsulfanyl)-3Ј-thiouridine 12 as a yellow
solid (0.217 g); δH [(CD3)2SO] 3.56 (1 H, dd, J 5.3 and 9.0), 3.62
(1 H, m), 3.82 (1 H, m), 4.22 (1 H, m), 4.43 (1 H, m), 5.28 (1 H,
m), 5.54 (1 H, d, J 8.1), 5.72 (1 H, d, J 2.0), 6.63 (1 H, d, J 5.4),
7.93 (1 H, d, J 8.2), 8.56 (1 H, d, J 9.0), 8.62 (1 H, dd, J 2.4 and
9.0), 8.90 (1 H, d, J 2.3), 11.34 (1 H, br s); δC [(CD3)2SO] 52.6,
59.7, 75.2, 84.2, 90.4, 101.2, 121.4, 128.2, 129.2, 140.3, 144.7,
145.0, 145.3, 150.4, 163.2.
Dry triethylamine (5.42 cm3, 39.0 mmol) and phosphorus
trichloride (1.05 cm3, 12.0 mmol) were added to a stirred solu-
tion of 1H-1,2,4-triazole (2.48 g, 36.0 mmol; recrystallised from
dry acetonitrile) in dry THF (72 cm3) at Ϫ35 ЊC (methanol–
solid CO2-bath). After 15 min, a solution of 3-N-benzoyl-2Ј,3Ј-
J. Chem. Soc., Perkin Trans. 1, 2000, 2227–2236
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