S. Ö lgen-Ch. K. Chu • 2'-Deoxy-2'-fluoro-L-arabinofuranosyl 1,2,3-Triazole Derivatives
808
rimeter. TLC were performed on Uniplates (silica
3,5-Di-0-benzoyl-2-deoxy-2-fluoro-ß-L-arabino-
gel) purchased from Analtech Co. Column chro- furanosyl azide (5b) and 3,5-di-O-benzoyl-
matography was performed using either Silica 2-deoxy-2-fluoro-a-L-arabinofuranosyl azide (5a)
Gel-60 (220-440 mesh) for flash chromatography
2
To a solution of 3 (7.5 g, 15.0 mmol) in CH
2
C1
or Silica Gel G (TLC grade > 440 mesh) for vac-
uum flash column chromatography. UV Spectra
were obtained on a Beckman DU 650 spectropho-
tometer. Elemental analyses were performed by
Atlantic Microlab, Inc., Norcross, GA.
(50 ml) was added HBr/AcOH (7 ml, 45% w/v),
and the mixture was stirred at rt overnight. After
usual work-up, 4 was obtained as a syrup which
was used directly for the next reaction without fur-
ther purification.
To a stirred solution of 4 in anhydrous DMF
(50 ml) was added NaN (10.7 g, 165 mmol), and
3
l,3,5-Tri-0-benzoyl-2-0-(2-imidazolylsulfonyl)-a-
the mixture was stirred at rt for 5 h. The solvent
was evaporated and the residue was extracted with
EtOAc (50 ml x 2), washed with water, and dried
over M gS04. Removal of solvent gave a syrup
which was separated by silica gel column chroma-
tography (10:1 hexanes-EtOAc). The fast moving
spot was collected to give 5a as an oil (1.3 g, 20%),
which upon standing became a wax-like solid. The
slow moving spot was collected and crystallized
from MeOH to give 5b as a white solid of (3.6 g,
57%).
L-ribofuranose (2)
To a stirred solution of 1 (22.5 g, 48.6 mmol) in
anhydrous CH
2
C12 (225 ml) and DMF (60 ml) at
-40 °C was added sulfuryl chloride (15.9 ml,
136.5 mmol) through a syringe. The resulting solu-
tion was stirred at -40 °C for 30 min and then
gradually warmed up to rt. After 3 h, imidazole
(48 g, 703.5 mmol) was added at 0 °C, and the mix-
ture was stirred at rt for 15 h. The hazy solution
was diluted with CH
ice-water, and the aqueous layer was extracted
again with CH C12. The combined organic layer
2
C12
(450 ml) and washed with
5a: M.p. 57-58 °C.
-
[a] ^ 5 -216.82° (c 0.3,
CHC13). - IR (film): v = 2116, 1727, 1603, 1585
cm -1. - ^C^H} NMR (CDC13): (3 = 166.58, 165.90
(C=0), 134.20,133.55,130.10,129.93,129.01,128.88,
128.80 (Ar), 98.13 (d, J = 184.4 Hz, 2'-C), 94.27
(d, J = 35.0 Hz, l'-C), 83.86 (4'-C), 77.45 (d, J =
2
was dried over M gS04. Removal of solvent and
purification by silicagel column chromatography
(5:1-1:1 hexanes-EtOAc) gave compound 2 as a
white solid (21.0 g, 73%). - lH NMR (CDC13):
<5= 7.00, 8.10 (m, 18H, A r-H ), 6.72 (d, / = 4.4 Hz,
1H, 1-H), 5.60 (dd, J = 6.5, 2.9 Hz, 1H, 3-H), 5.26
(dd, J = 4.5, 6.2 Hz, 1H, 2-H), 4.58, 4.80 (m, 3H,
4-H and 5-H).
30.7 Hz, 3'-C), 64.11 (5'-C).
C
1 9
H
1 6FN 0 5-
3
0.2H20 (385.35): calcd. C 58.67, H 4.25, N 10.80;
found C 58.85, H 4.16, N 10.44.
5b: M.p. 85 °C. - [a]fe 52.94° (c 0.4, CHC13). -
5
IR (film): v = 2124, 1725, 1603, 1586 cm"1. -
^C^H} NMR (CDC13): <5 = 166.59, 165.68 (C=0),
134.36, 133.64, 130.26, 130.20, 129.98, 128.89, 128.83
(Ar), 94.30 (d, J = 197.0 Hz, l'-C), 89.76 (d, J = 17.1
Hz, 2'-C), 80.59 (4'-C), 76.54 (d, J = 21A Hz, 3'-C),
l,3,5-Tri-0-benzoyl-2-deoxy-2-fluoro-a-L-
arabinofuranose (3)
64.35 (5'-C).
C 59.22, H 4.19, N 10.90; found C 59.18, H 4.27,
N 10.72.
-
C
1 9
H
1 6 FN
3
0
5
(385.35): calcd.
A suspension of 2 (20.9 g, 35.2 mmol) and KHF
(11.1 g, 141.6 mmol) in 2,3-butanediol (180 ml)
was stirred under N at 160 °C. To this was added
2
2
H F -H 20 (48%, 5.1 ml, 141.6 mmol), and the mix-
ture was stirred at 160 °C for 1 h. It was quenched
Ethyl triphenylphosphoranylidenepyruvate (
6
)
by brine-ice and then extracted with CH
75 ml). The combined extract was washed with
brine, water and saturated N aH C 0 respectively.
The organic layer was dried over M gS0 and
2
C12 (4 x
To stirred solution of triphenylphosphine
a
(19.0 g, 72 mmol) in THF (150 ml) was added
ethyl bromopyruvate (5.0 ml, 36 mmol), and the
3
4
treated with charcoal. It was put on a silica gel pad mixture was stirred at rt for 30 min and then re-
fluxed under argon for 2 h. The solvent was re-
moved under reduced pressure and the residue
(5 cm x 5 cm), eluted with CH
which was recrystallized from 95% EtOH to give
2
C1
2
to give a syrup
compound 3 (10.5 g, 64%). - *HNMR (CDC13): was triturated with Et20 (50 ml x 3), redissolved
<5= 7.38, 8.11 (m, 15H, Ar-H), 6.76 (d, J = 9.2 Hz, in water (200 ml) and extracted with Et20 (50 ml
x 2). The pH of the aqueous layer was adjusted
(d, FH/ = 48.3 Hz, 1H, 2-H), 4.65, 4.81 (m, 3H, with saturated N aH C 0 to ca. when no more
precipitate formed. It was filtered and the filter
1H, 1-H), 5.63 (dd, J = 2.9, 16.6 Hz, 1H, 3-H), 5.39
3
8
4-H and 5-H).
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