Jul-Aug 2007
Syntheses of Acyclic C-Glycosidic Derivatives of 1,2,4-Triazoles by Cycloadditions
935
General procedure for the preparation of acyclated
(CDCl ): ꢁ = 1.15 (d, J= 6.9 Hz, 6H, isopropyl-CH , 1.97, 2.03,
3
3
glycosidies (9). A solution of SbCl (2.99 g, 10 mmol) in CH Cl
2.05, 2.09, 2.10 (5 singlets, 5 Ac), 2.24 (s, CH ), 4.06 (dd, H-
5
2
2
3
(
20 ml) was added dropwise to a cold (-60 °C) solution of 2 (10
5",J4',5" = 5.69 Hz, J5',5"= 12.48 Hz), 4.49 (sept., isopropyl-CH),
4.59 (dd, H-5', J4',5' = 3.00 Hz), 5.30 (m, H-4'), 5.55 (dd, H-3',
J3',4' = 8.09 Hz), 5.93 (dd, H-2', J2',3' = 3.01 Hz), 6.17 (d, H-1',
J1',2' = 7.78 Hz). MS (FAB): m/z 486 [M+1]. Calcd. for
C H N O (485.50): C, 51.95; H, 6.44; N, 8.66. Found: C,
mmol) and the penta-O-acetyl-D-glucononitrile 5 (10 mmol) in
CH Cl (30 ml). The reaction mixture was stirred at –60 °C for
1
2
2
h, then between –30 and 0 °C for 3 h, and finally between 0
and 25°C for 1 h. The solvent was evaporated and the residue
2
1
31
3
10
was dissolved in CH CN (70 ml). At 0 °C an aqueous solution
51.96; H, 6.22; N, 8.93.
3
of NaHCO (3.36 g, 40 mmol) in H O (40 ml) was added and the
Preparations of free C-glycosidic compounds (10). Dry
gaseous ammonia was passed at 0 °C for about 1 h into a
solution of a nucleoside 9 (10 mmol) in dry MeOH (20 ml).
Then, the mixture was stirred at 23 °C until the reaction was
judged to be complete by TLC. Evaporation at 40 °C under
reduced pressure afforded the free C-glycosides 10.
3
2
mixture was stirred at room temperature for 1 h. The organic
layer was separated and the aqueous layer was extracted with
ethyl acetate (2 x 50 ml). The combined organic layers were
dried over Na SO and evaporated after filtration. Purification
2
4
by column chromatography (SiO ; eluent CHCl /MeOH 9:1)
2
3
afforded compounds 9.
,2,3,4,5-Penta-O-acetyl-1-(5,6,7,8-tetrahydro-[1,2,4]-tria-
zolo[1,5-a]pyridin-2-yl)-D-arabinitol (9a). Yield 3.43 g (71%)
1-(5,6,7,8-Tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-D-
arabinitol (10a). Yield 1.99 g (73%) of a foam. IR (KBr): ꢀ
1
-1
1
(cm ) 3222 (OH), 1608 (C=N); H NMR (DMSO-d ): ꢁ = 1.91
6
-1
1
as an oil. IR (KBr): ꢀ (cm ) 1757 (C=O), 1603 (C=N). H NMR
(m, 2 CH ), 2.79 (m, 2 CH ), 3.45 (dd, H-5", J = 6.15 Hz, J5',5"
2
2
4',5"
(
2
CDCl ): ꢁ = 1.88 (m, 4 CH ), 1.99 - 2.11 (5 singlets, 5 Ac),
= 11.86 Hz), 3.60 (t, H-5'), 3.47 (t, H-4', J4',5' = 2.80 Hz), 3.77 (t,
H-3', J3',4' = 8.00 Hz), 4.07 (dd, H-2', J2',3' = 1.58 Hz), 4.09 (m,
3
2
.66 (m, CH ), 3.98 (m, CH ), 4.03 (dd, H-5", J
= 5.76 Hz,
4',5"
2
2
J5',5" = 12.35 Hz), 4.59 (dd, H-5', J4',5' = 3.00 Hz), 5.29 (m, H-4'),
CH ), 4.20 (d, OH-3', J
= 7.40 Hz), 4.23 (dd, H-1', J1',2' =
2
3'-OH
5
6
.60 (dd, H-3', J3',4' = 8.15 Hz), 5.38 (dd, H-2', J2',3' = 3.06 Hz),
.37 (d, H-1', J1',2' = 7.80 Hz). MS (FAB): m/z 484 [M+1].
8.40 Hz), 4.31 (t, OH-5', J5'-OH = 5.58 Hz), 4.32 (d, OH-2', J2'-OH
= 6.1 Hz), 4.34 (d, OH-4', J = 5.60), 5.19 (d, OH-1', J1'-OH
5.50 Hz); H NMR (DMSO-d + D O): ꢁ = 1.93 (m, 2 CH ), 2.81
6 2 2
=
4'-OH
1
Calcd. for C H N O (483.48): C, 52.17; H, 6.05; N, 8.69.
21
29
3
10
Found: C, 52.19; H, 6.07; N, 8.69
,2,3,4,5-Penta-O-acetyl-1-(6,7,8,9-tetrahydro-5H-[1,2,4]-
triazolo[1,5-a]azepin-2-yl)-D-arabinitol (9b). Yield 3.03 g
(m, CH ), 3.45 (dd, H-5", J = 6.15 Hz, J5',5" = 11.86 Hz), 3.60
2 4',5"
1
(t, H-5'), 3.47(t, H-4', J4',5' = 2.80 Hz), 3.77 (t, H-3', J3',4' = 8.00
Hz), 4.10 (m, CH ), 4.01 (dd, H-2', J = 1.58 Hz), 4.23 (dd, H-
2
2',3'
-
1
13
(
61%) as an oily product; IR (KBr) ꢀ (cm ): 1759 (C=O), 1601
1', J1',2' = 8.40 Hz); C NMR (DMSO-d ): ꢁ= 19.9, 22.3, 23.0,
6
1
(C=N); H NMR (CDCl ): ꢁ= 1.45 (m, CH ), 1.51 (m, CH ),
47.2 (CH ), 66.1 (C-1'), 70.9 (C-2'), 70.5 (C-3'), 71.4 (C-4'), 63.7
3
2
2
2
1
.60 (m, CH ), 1.98- 2.11 (5 singlets, 5 Ac), 2.64 (m, CH ), 3.94
(C-5'), 158.7 (C-5), 160.1 (C-3). MS (FAB): m/z 274 [M+1].
2
2
(
m, CH ), 4.01 (dd, H-5", J = 5.68 Hz, J5',5" = 12.40 Hz), 4.55
Calcd. for C H N O (273.29): C, 48.35; H, 7.01; N, 15.38.
2
4',5"
11 19
3
5
(
8
7
dd, H-5', J4',5' = 2.99 Hz), 5.27 (m, H-4'), 5.58 (dd, H-3', J3',4'
.37 Hz), 5.31 (dd, H-2', J2',3' = 3.00 Hz), 6.32 (d, H-1', J1',2'
=
=
Found: C, 48.38; H, 7.05; N, 15.39.
1-(6,7,8,9-Tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-yl)-
D-arabinitol (10b). Yield 1.75 g (61%); mp 79-81 °C; IR (KBr) ꢀ
.79 Hz). MS (FAB): m/z 498 [M+1]. Calcd. for C H N O
2
2
31
3
10
-1
1
(497.51): C, 53.11; H, 6.28; N, 8.45. Found: C, 53.10; H, 6.30;
(cm ): 3230 (OH), 1603 (C=N); H NMR (D O): ꢁ = 1.58 (m,
2
N, 8.46.
CH ), 1.66 (m, CH ), 1.80 (t, CH ), 2.82 (t, CH ), 3.49 (dd, H-5",
2
2
2
2
1
,2,3,4,5-Penta-O-acetyl-1-(1,5-dimethyl-1H-1,2,4-triazol-
J4',5" = 6.10 Hz, J5',5" = 11.80 Hz), 3.59 (t, H-5'), 3.46 (t, H-4', J4',5' =
3
-yl)-D-arabinitol (9c). Yield 3.24 g (71%); m.p. 80-82 °C; IR
2.80 Hz), 3.77 (dd, H-3', J3',4' = 8.01 Hz), 4.00 (dd, H-2', J2',3' = 1.60
Hz), 4.06 (t, CH ), 4.36 (dd, H-1', J = 8.38 Hz). MS (FAB): m/z
-1
1
(KBr) ꢀ (cm ): 1757 (C=O), 1601 (C=N); H NMR (CDCl ): ꢁ=
3
2
1',2'
1
3
4
.99, 2.05, 2.06, 2.09, 2.10 (5 singlets, 5 Ac), 2.17 (s, CH ),
288 [M+1]. Calcd. for C H N O (287.32): C, 50.17; H, 7.37; N,
12 21 3 5
14.63. Found: C, 49.99; H, 7.30; N, 14.65.
3
.51(s, CH ), 4.00 (dd, H-5", J
= 5.78 Hz, J5',5"= 12.40 Hz),
4',5"
3
.57 (dd, H-5', J4',5'= 3.19 Hz), 5.25 (m, H-4'), 5.61 (dd, H-3',
1-(1,5-Dimethyl-1H-1,2,4-triazol-3-yl)-D-arabinitol (10c).
-
1
J3',4' = 8.07 Hz), 5.85 (dd, 1H, J = 3.00 Hz, H-2'), 6.30 (d, 1H,
J1',2' = 7.81 Hz, H-1'); C NMR (CDCl ): ꢁ= 20.53, 20.64, 20.82,
Yield: 1.38 g (56%); mp 140-142 °C; IR (KBr) ꢀ (cm ): 3210
2',3'
13
1
3
(OH), 1601 (C=N); H NMR (D O): ꢁ = 2,33 (s, CH ), 3.60 (dd,
2
3
(
3
1
Ac), 11.18, 34.80 (CH ), 67.79 (C-1'), 69.97 (C-2'), 68.70 (C-
'), 68.29 (C-4'), 61.98 (C-5'),145.95 (C-5), 157.88 (C-3),
69.61, 169.78, 169.99, 170.80 (CO). MS (FAB): m/z 458
H-5", J4',5" = 6.2 Hz, J5',5" = 12.2 Hz), 3.69 (t, H-4', J4',5' = 2.80
Hz), 3.65 (t, H-5'), 3.81 (dd, H-3', J3',4'= 8.3 Hz), 3.69 (s, N-
3
CH ), 4.03 (dd, H-2', J2',3'= 1.60 Hz), 4.06 (d, H-1', J1',2' = 8.40
3
[
M+1]. Calcd. for C H N O (457.44): C, 49.89; H, 5.95; N,
Hz). MS (FAB): m/z 248 [M+1]. Calcd for C H N O (247.25):
19
27
3
10
9
17
3
5
9
.19. Found: C, 49.91; H, 5.98; N, 9.20.
,2,3,4,5-Penta-O-acetyl-1-(1-ethyl-5-methyl-1H-1,2,4-tria-
zol-3-yl)-D-arabinitol (9d). Yield 3.11 g (66%); m.p. 79-81 °C;
C, 43.72; H, 6.93; N, 16.99. Found: C, 43.52; H, 6.84; N, 16.86.
1
1-(1-Ethyl-5-methyl-1H-1,2,4-triazol-3-yl)-D-arabinitol (10d).
-
1
Yield: 1.52 g (58%); m.p. 114-116 °C; IR (KBr) ꢀ (cm ): 3210
-1
1
1
IR (KBr) ꢀ (cm ): 1756 (C=O), 1602 (C=N); H NMR (CDCl ):
(OH), 1601 (C=N); H NMR (D O): ꢁ = 1.37 (t, ethyl-CH ), 2.60
3
2
3
ꢁ
= 1.07 (t, 3H, ethyl-CH ), 1.98, 2.01, 2.06, 2.08, 2.09 (5
(s, CH ), 3.60 (dd, H-5", J = 6.40 Hz, J5',5" = 12.00 Hz), 3.68
3 4',5"
3
singlets, 5 Ac), 2.19 (s, CH ), 3.80 (q, J= 7.0 Hz, ethyl-CH ),
(t, H-4', J4',5' = 2.80 Hz), 3.71 (t, H-5'), 3.78 (dd, H-3', J3',4' = 8.20
Hz), 4.02 (dd, H-2', J2',3' = 1.60 Hz), 4.20 (q, N-CH , J= 7.0),
4.81 (d, H-1', J1',2' = 8.20 Hz). MS (FAB): m/z 262 [M+1]. Calcd
3
2
4
.03 (dd, H-5", J4',5" = 5.78 Hz, J5',5" = 12.55 Hz), 4.53 (dd, H-5',
J4',5' = 3.12 Hz), 5.28 (m, H-4'), 5.60 (dd, H-3', J3',4' = 8.09 Hz),
.75 (dd, H-2', J2',3' = 3.01 Hz), 6.29 (d, H-1', J1',2' = 7.79 Hz).
MS (FAB): m/z 472 [M+1]. Calcd. for C H N O (471.4): C,
2
5
for C H N O (261.32): C, 45.97; H, 7.33; N, 16.08. Found: C,
10
19
3
5
45.72; H, 7.19; N, 16.19.
20
29
3
10
5
0.95; H, 6.20; N, 8.91. Found: C, 50.95; H, 6.22; N, 8.92.
,2,3,4,5-Penta-O-acetyl-1-(1-isopropy-5-methyl-1H-1,2,4-
triazol-3-yl)-D-arabinitol (9e). Yield 3.79 g (78%); m.p. 65-67
1-(1-Isopropy-5-methyl-1H-1,2,4-triazol-3-yl)-D-arabinitol
-1
1
(10e). Yield: 1.82 g (66%); foam; IR (KBr) ꢀ (cm ): 3210 (OH),
1
1601 (C=N); H NMR (D O): ꢁ = (D O): 1.10 (d, 6H, isopropyl-
2
2
-1
1
°
C; IR (KBr) ꢀ (cm ): 1755 (C=O), 1601 (C=N); H NMR
3
3
CH ), 2.19 (s, CH ), 3.57(dd, H-5", J4',5" = 6.79 Hz, J5',5" = 11.80