A.C.N. de Melo et al.: Anti-inflammatory 2,3-unsaturated O-glycosidesꢀꢂꢁꢁꢁꢀ5
2
1.5, 30.8, 64.3, 66.6, 68.6, 70.6, 95.8, 125.2, 126.7, 128.1, 129.6, 130.4, General procedure for synthesis of 2,3-dideoxy-hex-
1
42.9, 171.3, 171.5. Anal. Calcd for C H O S: C, 56.46; H, 5.92. Found:
16
20
6
2-enopyranosides
C, 56.57; H, 6.01.
A mixture of the acetylated compound 3b,c or 5b,c in a mixed solvent
(
1R,2S,5R)-Menthyl
4,6-di-O-acetyl-2,3-didesoxy-α-D-erythro-
of MeOH/H O/Et N (9ꢀ:ꢀ6ꢀ:ꢀ1) was stirred at room temperature for 2 h (for
hex-2-enopyranoside (3d)ꢁYield 82% (method A); yield 71%
2
3
2
0
6b,c) or 3 h (for 7b) or 4 h (for 7a and 7c). TLC plates were developed
(
method B); colorless oil; R 0.6 (5% EtOAc/CH Cl ); [α] ꢀ+ꢀ44° (c 1,
f 2 2 D
2
0
1
using methanol/CHCl (1ꢀ:ꢀ9). The solvent was removed under reduced
3
CH Cl ); [α] ꢀ+ꢀ46° (c 0.75, CH Cl ) [23]. The H NMR spectrum is virtu-
2
2
D
2
2
pressure and the residue was subjected to silica gel column chroma-
tography eluting with a mixed solvent of ethyl acetate/hexane (4ꢀ:ꢀ5).
ally identical with previously reported data [26].
Benzyl 4,6-di-O-acetyl-2,3-didesoxy-α-D-threo-hex-2-enopyra-
noside (5a)ꢁYield 82% (method A); yield 78% (method B); colorless
2
-(Thiophene-3-yl)ethyl 2,3-dideoxy-α-D-erythro-hex-2-enopyra-
noside (6b)ꢁYield 87%; colorless oil; R 0.5 (10% EtOAc/CHCl );
): δ 2.91 (t, 2H, Jꢀ=ꢀ6.9 Hz,
CH -Het), 3.59–3.80 (m, 5H, 2xOH, OCH , H-4, H-5), 3.94–4.05 (m,
2
0
20
f
3
oil. R 0.8 (10% EtOAc/CH Cl ); [α] ꢀ−ꢀ134° (c 2, CHCl ); [α] ꢀ−ꢀ83° (c
f
2
2
D
3
D
2
0
1
1
[α] ꢀ+ꢀ29° (c 0.7, CHCl ); H NMR (acetone-d
D 3 6
0
.27, CHCl ). The H NMR spectrum is virtually identical with previ-
ously reported details [12].
3
2
2
3
H, OCH , H-6, H-6′), 4.96 (br dd, 1H, Jꢀ=ꢀ2.7 Hz and 1.2 Hz, H-1), 5.67
2
(
ddd, 1H, Jꢀ=ꢀ10.2 Hz, 2.7 Hz and 1.8 Hz, H-2), 5.88 (ddd, 1H, Jꢀ=ꢀ10.2 Hz,
2
-(Thiophene-3-yl)ethyl 4,6-di-O-acetyl-2,3-dideoxy-α-D-threo-
1
.8 Hz and 1.8 Hz, H-3), 7.04 (dd, 1H, Jꢀ=ꢀ5.1 Hz and 1.2 Hz, Ar-H ),
hex-2-enopyranoside (5b)ꢁYield 60% (method A); yield 54%
a
1
3
2
0
7.15–7.18 (m, 1H, Ar-H
c
), 7.54 (dd, 1H, Jꢀ=ꢀ5.1 Hz and 3.0 Hz, Ar-H
b
);
C
(
method B); colorless oil. R 0.7 (5% EtOAc/CH Cl ); [α] ꢀ−ꢀ101° (c 2,
f 2 2 D
1
NMR (acetone-d ): δ 30.8, 61.9, 63.4, 68.5, 72.8, 94.5, 121.4, 125.5, 125.9,
6
CHCl ). H NMR (acetone-d ): δ 1.98 (s, 3H, CH CO), 2.02 (s, 3H, CH CO),
3
6
3
3
1
29.0, 134.4, 139.9. Anal. Calcd for C H O S (1/4H O): C, 55.26; H, 6.38.
12 16 4 2
2
.94 (t, 2H, Jꢀ=ꢀ6.9 Hz, CH -Het), 3.74 (dt, 1H, Jꢀ=ꢀ9.6, 6.9 Hz, OCH ), 3.99
2
2
Found: C, 55.25; H, 6.56.
(
dt, 1H, Jꢀ=ꢀ9.6, 6.9 Hz, OCH ), 4.13 (dd, 1H, Jꢀ=ꢀ11.4 Hz and 7.8 Hz, H-6
2
or H6′), 4.20 (dd, 1H, Jꢀ=ꢀ11.4 Hz and 4.8 Hz, H-6 or H6′), 4.29 (ddd, 1H,
Jꢀ=ꢀ7.8 Hz, 4.8 Hz and 2.4 Hz, H-5), 5.00 (dd, 1H, Jꢀ=ꢀ4.8 Hz and 2.4 Hz,
H-4), 5.08 (brd, 1H, Jꢀ=ꢀ1.5 Hz, H-1), 6.04 (dd, 1H, Jꢀ=ꢀ11.1 Hz and 0.9 Hz,
H-2 or H-3), 6.05 (d, Jꢀ=ꢀ11.1, 1H, H-2 or H-3), 7.05 (dd, 1H, Jꢀ=ꢀ5.1 Hz
and 1.2 Hz, Ar-H ), 7.17–7.19 (m, 1H, Ar-H ), 7.38 (dd, 1H, Jꢀ=ꢀ5.1 Hz and
2
-(Thiophene-2-yl)ethyl 2,3-dideoxy-α-D-erythro-hex-2-enopyra-
noside (6c)ꢁYield 75%; colorless solid; mp 68–69°C. R 0.5 (EtOAc/
f
2
0
1
CHCl 1;9); [α]D ꢀ+ꢀ51° (c 1, CHCl ); H NMR (acetone-d ): δ 3.10 (td,
3,
3
6
2
H, Jꢀ=ꢀ6.6 Hz and 1.2 Hz, CH -Het), 3.62–3.73 (m, 4H, 2xOH, OCH ,
2
2
a
c
1
3
H-4), 3.80 (ddd, 1H, Jꢀ=ꢀ11.4 Hz, 4.8 Hz and 2.1 Hz, H-5), 3.97–4.08
m, 2H, OCH , H-6 or H-6′), 4.98 (br d, 1H, Jꢀ=ꢀ2.7 Hz, H-1), 5.68 (ddd,
2
.7 Hz, Ar-H ); C NMR (acetone-d ): δ 21.3 (2C), 32.0, 64.1 (2C), 68.4,
c
6
(
6
9.6, 95.4, 122.6, 126.4, 126.7, 130.0, 132.3, 141.0, 171.2, 171.4. Anal. Calcd
2
1
H, Jꢀ=ꢀ10.2 Hz, 4.8 Hz and 2.7 Hz, H-2), 5.90 (dd, 1H, Jꢀ=ꢀ10.2 Hz and
.7 Hz, H-3), 6.89–6.94 (m, 2H, Ar-H and H ), 7.23 (dd, 1H, Jꢀ=ꢀ5.4 Hz
for C H O S: C, 56.46; H, 5.92. Found: C, 56.36; H, 5.73.
1
6
20
6
2
a
b
1
3
and 1.5 Hz, Ar-H ); C NMR (acetone-d ): δ 31.2, 63.0, 64.5, 69.5, 73.4,
c
6
2
-(Thiophene-2-yl)ethyl 4,6-di-O-acetyl-2,3-dideoxy-α-D-threo-
9
5.2, 124.4, 126.0, 126.5, 127.4, 134.9, 142.4. Anal. Calcd for C H O S: C,
12 16 4
hex-2-enopyranoside (5c)ꢁYield 53% (method A); yield 50%
5
6.23; H, 6.29. Found: C, 56.03; H, 5.92.
2
0
(
method B); colorless oil. R 0.7 (5% EtOAc/CH Cl ); [α] ꢀ−ꢀ121° (c
f
2
2
D
1
1
, CHCl ); H NMR (acetone-d ): δ 1.98 (s, 3H, CH CO), 2.02 (s, 3H,
3
6
3
Benzyl 2,3-didesoxy-α-D-threo-hex-2-enopyranoside (7a)ꢁYield
CH CO), 3.14 (t, 2H, Jꢀ=ꢀ6.9 Hz, CH -Het), 3.74 (dt, 1H, Jꢀ=ꢀ9.9 Hz and
o
3
2
60%; colorless crystals; mp 102–103 C. R 0.5 (EtOAc/CHCl , 1:9);
f
3
6
.9 Hz, OCH ), 4.00 (dt, 1H, Jꢀ=ꢀ9.9 Hz and 6.9 Hz, OCH ), 4.15 (dd, 1H,
20
o
1
2
2
[α]D ꢀ−ꢀ106 (c 1, CHCl ); H NMR (acetone-d ): δ 2.85 (brs, 2H, OH),
3
6
Jꢀ=ꢀ11.4 Hz and 7.8 Hz, H-6 or H-6′), 4.21 (dd, 1H, Jꢀ=ꢀ11.4 Hz and 4.8 Hz,
H-6 or H-6′), 4.32 (ddd, 1H, Jꢀ=ꢀ7.8 Hz, 4.8 Hz and 2.7 Hz, H-5), 5.02
3
.68–3.81 (m, 2H, H-6 and H-6′), 3.85 (ddd, 1H, Jꢀ=ꢀ5.4 Hz, 2.4 Hz and
2
.4 Hz, H-5), 4.04 (dd, 1H, Jꢀ=ꢀ6.0 Hz and 2.4 Hz, H-4), 4.55 (d, 1H,
(
brdd, 1H, Jꢀ=ꢀ4.4 Hz and 2.7 Hz, H-4), 5.10 (br d, 1H, Jꢀ=ꢀ1.5 Hz, H-1)),
.06 (s, 1H, H-2 or H-3), 6.07 (d, Jꢀ=ꢀ1.2, 1H, H-2 or H-3), 6.91–6.95 (m,
Jꢀ=ꢀ11.8 Hz, OCH Ph), 4.82 (d, 1H, Jꢀ=ꢀ11.8 Hz, OCH Ph), 5.07 (brd, 1H,
2
2
6
Jꢀ=ꢀ3.0 Hz, H-1), 5.86 (dd, 1H, Jꢀ=ꢀ9.9 Hz and 3.0 Hz, H-2), 6.09 (dd, 1H,
1
3
2
H, Ar-H and Ar-H ), 7.25 (dd, 1H, Jꢀ=ꢀ5.1 Hz and 1.2 Hz, Ar-H );
C
13
a
b
c
Jꢀ=ꢀ9.9 Hz and 6.0 Hz, H-3), 7.25–7.40 (m, 5H, Ar-H); C NMR (acetone-
NMR (acetone-d ): δ 20.6, 20.7, 31.1, 63.4, 63.5, 67.8, 69.5, 94.8, 124.5,
6
d6): δ 62.1, 62.6; 69.7, 72.6, 94.2, 128.2, 128.7, 128.8 (2C), 129.0 (2C),
1
25.8, 126.0, 127.5, 131.5, 142.1, 170.6, 170.7. Anal. Calcd for C H O S: C,
16 20 6
130.8, 139.5. Anal. Calcd for C H O : C, 66.09; H, 6.83. Found: C,
1
3
16
4
5
6.46; H, 5.92. Found: C, 56.49; H, 6.18.
6
5.56; H, 6.76.
(
1R,2S,5R)-Menthyl 4,6-di-O-acetyl-2,3-dideoxy-α-D-threo-hex- 2-(Thiophene-3-yl)ethyl 2,3-dideoxy-α-D-threo-hex-2-enopyra-
-enopyranoside (5d)ꢁYield 72% (method A); yield 65% (method noside (7b)ꢁYield 62%; colorless oil; R 0.5 (10% EtOAc/CHCl );
2
f
3
2
5
20
o
1
B); colorless solid from EtOAc/hexane; mp 65–67°C; [α] ꢀ−ꢀ200° (c [α] ꢀ−ꢀ91 (c 0.7, CHCl ); H NMR (acetone-d ): δ 2.89 (t, 2H, Jꢀ=ꢀ6.9 Hz,
1
D
D
3
6
2
0
1
, CH Cl ); [α] ꢀ−ꢀ159° (c 0.16, CH Cl ) [21]; H NMR (CDCl ): δ 0.77 (d, CH -Het), 3.63–3.83 (m, 6H, 2xOH, OCH , H-5, H-6, H-6′), 3.91–4.04
2 2 D 2 2 3
2
2
3
H, Jꢀ=ꢀ7.1 Hz, CH , menthyl), 0.90 (2d, 6H, Jꢀ=ꢀ7.0 and 6.5 Hz, 2CH , (m, 2H, OCH , H-4), 4.97 (br d, 1H, Jꢀ=ꢀ3.0 Hz, H-1), 5.81 (ddd, 1H,
3
3
2
menthyl), 0.80–1.65 (m, 8H, menthyl), 2.06 (s, 3H, CH CO), 2.07 (s, Jꢀ=ꢀ10.2 Hz, 3.0 Hz and 0.6 Hz, H-2), 6.05 (ddd, 1H, Jꢀ=ꢀ10.2 Hz, 5.4 Hz
3
3
1
H, CH CO), 2.20 (bd, 1H, Jꢀ=ꢀ12.3 Hz, menthyl), 3.43 (ddd, pseudo-td, and 1.2 Hz, H-3), 7.04 (dd, 1H, Jꢀ=ꢀ4.8 Hz and 1.2 Hz, Ar-H ), 7.17 (m, 1H,
3
a
1
3
H, Jꢀ=ꢀ10.6 Hz, 10.6 Hz and 4.1 Hz, menthyl), 4.18 (dd, 1H, Jꢀ=ꢀ11.5 Hz Ar-H ), 7.35 (dd, 1H, Jꢀ=ꢀ4.8 Hz and 3.0 Hz, Ar-H ); C NMR (CDCl ): δ
c
b
3
and 7.6 Hz, H-6 or H-6′), 4.23 (dd, 1H, Jꢀ=ꢀ11.5 Hz and 5.0 Hz, H-6 or 32.1, 64.5, 64.7, 68.2, 73.2, 95.8, 122.5, 126.9, 129.5, 130.0, 131.5, 141.1.
H-6′), 4.40 (ddd, 1H, Jꢀ=ꢀ7.6 Hz, 5.0 Hz and 2.6 Hz, H-5), 5.00 (dd, 1H, Anal. Calcd for C H O S: C, 56.23; H, 6.29. Found: C, 55.77; H, 6.02.
1
2
16
4
Jꢀ=ꢀ4.7 Hz and 2.6 Hz, H-4), 5.13 (br d, 1H, Jꢀ=ꢀ2.4 Hz, H-1), 6.03 (dd, 1H,
Jꢀ=ꢀ10.0 Hz and 2.4 Hz, H-2), 6.09 (dd, 1H, Jꢀ=ꢀ10.0 Hz and 4.7 Hz, H-3); 2-(Thiophene-2-yl)ethyl 2,3-dideoxy-α-D-threo-hex-2-enopyra-
1
3
C NMR (CDCl ): δ 16.2, 20.8, 21.1, 22.4, 23.1, 25.6, 31.7, 34.3, 43.2, 48.9, noside (7c)ꢁYield 53%; colorless oil; R 0.5 (10% EtOAc/CHCl );
3
f
3
2
0
o
1
6
3.0, 63.2, 66.6, 80.7, 95.6, 124.7, 130.7, 170.3, 170.6.
[α] ꢀ−ꢀ144 (c 0.8, CHCl ); H NMR (acetone-d ): δ 3.10 (td, 2H, Jꢀ=ꢀ6.6,
D 3 6
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