Paper
RSC Advances
ꢀ
1
1
13
1
7
443, 1373, 1227, 1145 cm ; H NMR (600 MHz, CDCl
3
) d 7.38– 2.78 (d, J ¼ 11.4 Hz, 1H, H-3), 1.75 (s, 3H, CH
3
) ppm; C NMR
.30 (m, 5H, Ph), 6.07 (d, J ¼ 1.8 Hz, 1H, H-1), 5.15–5.14 (m, 1H, (150 MHz, CDCl ) d 168.8 (C), 136.7 (C), 128.6 (CH ꢃ 2), 128.3
3
H-4), 5.02–5.02 (m, 1H, H-2), 4.78 (d, J ¼ 2.4 Hz, 1H, H-5), 4.75 (CH), 127.8 (CH ꢃ 2), 123.4 (CH), 96.7 (CH), 75.7 (CH), 72.9
(
d, J ¼ 11.4 Hz, 1H, CH Ph), 4.72 (d, J ¼ 11.4 Hz, 1H, CH Ph), (CH), 72.8 (CH ), 71.7 (CH), 66.9 (CH), 52.4 (CH ), 50.2 (CH ),
2
2
2
3
3
+
3
2
1
2
7
.95 (t, J ¼ 3.0 Hz, 1H, H-3), 3.76 (s, 3H, CO
2
Me), 2.10 (s, 3H, Ac), 24.3 (CH
3
) ppm. HRMS (M + Na ) calcd for C17
H
22
O
8
Na
1
3
.09 (s, 3H, Ac), 2.02 (s, 3H, Ac) ppm; C NMR (150 MHz, CDCl
3
)
377.1207, found: 377.1211.
69.7 (C), 169.6 (C), 168.4 (C), 167.2 (C), 136.5 (C), 128.5 (CH ꢃ
Methyl 3-O-benzyl-4-O-chloroacetyl-b-L-idopyranuronate-1,2-
), (methylorthoacetate) (16). DCM (15 mL) and compound 15 (374
), 20.7 mg, 1.05 mmol) were charged into a round bottom ask under a
), 128.2 (CH), 127.8 (CH ꢃ 2), 89.8 (CH), 73.2 (CH), 72.9 (CH
2
2.7 (CH), 67.0 (CH), 65.0 (CH), 52.5 (CH), 20.7 (CH
3
+
ꢁ
(
CH ), 20.5 (CH ) ppm. HRMS (M + Na ) calcd for C H O Na nitrogen atmosphere then cooled to 0 C. Pyridine (422 mL, 5.25
3
3
20 24 10
4
47.1262, found: 447.1276.
Methyl
methyl-orthoacetate) (14). TiBr
mmol) was subsequently added to the reaction mixture and
ꢁ
4-O-acetyl-3-O-benzyl-b-L-idopyranuronate-1,2- then cooled to ꢀ20 C. A solution of chloroacetyl chloride (333
(
4
(106 mg, 0.23 mmol) was mL, 4.2 mmol) was slowly charged into the reaction mixture at
ꢁ
added to a solution of 13 (100 mg, 0.18 mmol) in CH
The resulting mixture was stirred at room temperature (30 C) mass was diluted with DCM (10 mL) and quenched into cold
2
Cl
2
(2 mL). ꢀ20 C. Aer stirring the reaction mixture for 12 h, the reaction
ꢁ
for 2 h and then diluted with CH
ice-cold water (5 mL). The organic layer was ltered through a and the organic layer was washed with a NaHCO
2
Cl
2
(10 mL), and washed with water (10 mL). The organic and aqueous layers were separated
solution and
3
Celite 545 pad, and the ltrate was ltered through a phase dried over magnesium sulfate. Aer evaporation, the residue
silicon-treated ltered, concentrated, giving methyl 1-bromo- was puried in a silica gel column using the solvent system
2,4-di-O-acetyl-3-O-benzyl-L-idofuranoate. A solution of methyl 20 : 80 : 1 (EtOAc–Hexane–Et3N) to afford 16 as a faint yellow
1
-bromo-2,4-di-O-acetyl-3-O-benzyl-L-idofuranoate in anhydrous solid (401 mg, 89%). R
f
¼ 0.4 (EtOAc–hexane ¼ 1/2); mp ¼ 120–
ꢁ
ꢀ1 1
DCM (2 mL) containing freshly distilled 2,4,6-trimethyl pyridine 121 C; IR (KBr) n 3607, 3089, 3002, 1752, 1497, 1329 cm ; H
(
150 mL) and methyl alcohol (140 mL) was then stirred for 2 days NMR (600 MHz, CDCl
3
) d 7.39–7.32 (m, 5H, Ph), 5.56 (d, J ¼ 2.4
ꢁ
at room temperature (30 C). The mixture was diluted with Hz, 1H, H-1), 5.24 (t, J ¼ 1.2 Hz, 1H, H-4), 4.81 (d, J ¼ 12.0 Hz,
dichloromethane (10 mL) and the resulting organic phase was 1H, CH
2
Ph), 4.67 (d, J ¼ 11.4 Hz, 1H, CH Ph), 4.57 (d, J ¼ 1.2 Hz,
2
washed with a saturated NaHCO solution (2 mL), ltered, and 1H, H-5), 4.15 (t, J ¼ 2.4 Hz, 1H, H-3), 4.07 (s, 1H, H-2), 4.05 (d, J
3
concentrated. The residue was puried by ash chromatog- ¼ 15.0, 1H, ClCH CO), 4.00 (d, J ¼ 15.0, 1H, ClCH CO), 3.79 (s,
2
2
1
3
raphy (EtOAc–hexane, 1 : 3 to 1 : 1) to give 14 (58 mg, 64% in two 3H, COOMe), 3.24 (s, 3H, OCH ), 1.71 (s, 3H, CH ) ppm;
C
3
3
2
8
steps) as light yellow oil. R
2.0 (c 1.0, CH Cl
440 cm ; H NMR (600 MHz, CDCl
.55 (d, J ¼ 3.0 Hz, 1H, H-1), 5.18–5.17 (m, 1H, H-4), 4.79 (d, J ¼ 49.2 (CH
2 Hz, 1H, CH Ph), 4.54 (d, J ¼ for C19
Ph), 4.67 (d, J ¼ 11.4 Hz, 1H, CH
.2 Hz, 1H, H-5), 4.12 (t, J ¼ 2.4 Hz, 1H, H-3), 4.07–4.06 (m, 1H, Methyl 2-O-acetyl-3-O-benzyl-4-O-(chloroacetyl)-2-O-acetyl-L-
f
¼ 0.5 (EtOAc–hexane ¼ 1/2); [a]
); IR (KBr) n 3552, 3031, 1763, 1472, 1505, (CH ꢃ 2), 128.4 (CH), 128.0 (CH ꢃ 2), 124.1 (CH), 96.5 (CH), 75.8
) d 7.37–7.30 (m, 5H, Ph), (CH), 73.0 (CH ), 71.0 (CH), 69.3 (CH), 68.3 (CH), 52.7 (CH ),
), 40.4 (CH ) ppm. HRMS (M + Na ) calcd
ClNa 453.0923, found: 453.0941.
D
¼
3
NMR (150 MHz, CDCl ) d 167.6 (C), 166.6 (C), 136.5 (C), 128.6
ꢀ
2
2
ꢀ1 1
1
5
1
1
3
2
3
+
3
2 3
), 24.9 (CH
2
2
23 9
H O
H-2), 3.77 (s, 3H, CO CH ), 3.23 (s, 3H, OCH ), 2.02 (s, 3H, idopyranuronate (17). Compound 16 (100 mg) was dissolved in
OCOCH ), 1.72 (s, 3H, CH ) ppm; C NMR (150 MHz, CDCl ) d a solution of AcOH–H O (2 mL, 9/1) and stirred for 30 min at 28
1
2
3
3
1
3
3
3
3
2
ꢁ
70.0 (C), 168.0 (C), 136.7 (C), 128.5 (CH ꢃ 2), 128.2 (CH), 127.9
C. Aer evaporation, the residue was puried in a silica gel
(
CH ꢃ 2), 124.1 (C), 96.5 (CH), 76.0 (CH), 72.8 (CH
2
), 71.2 (CH), column using the solvent system 1 : 3 (EtOAc–toluene) to afford
), 24.9 (CH ), 20.6 product 17 (90 mg, 94%) as a colourless oil (b/a mixture). R
Na 419.1313, 0.2 (EtOAc–hexane ¼ 1/2). IR (KBr) n 3607, 3089, 3002, 1752,
6
9.5 (CH), 66.7 (CH), 52.5 (CH
3
), 49.0 (CH
) ppm. HRMS (M + Na ) calcd for C19
found: 419.1316.
3
3
f
¼
+
(
CH
3
24 9
H O
ꢀ1 1
3
1497, 1329 cm ; H NMR (600 MHz, CDCl ) d 7.39–7.31 (m, 5H,
Methyl 3-O-benzyl-b-L-idopyranuronate 1,2-(methylortho- Ph), 5.31 (d, J ¼ 7.2 Hz, 1H, H-1b), 5.27–5.26 (m, 1H, H-2a), 5.18–
acetate) (15). Compound 14 (1.59 g, 0.55 mmol) was dissolved in 5.17 (m, 1H, H-1a), 5.03 (d, J ¼ 1.8 Hz, 1H, H-4a), 4.92–4.91 (m,
ꢁ
methanol (20 mL) and cooled to ꢀ0 C. A 0.5 M solution NaOMe 0.6H, H-5a), 4.83–4.82 (m, 1H, H-5b), 4.77 (s, 1H, CH Ph), 4.74
2
(
6.40 mL) was added, and the reaction mixture was stirred at (s, 0.6H, H-4b), 4.39 (d, J ¼ 8.4 Hz, 1H, H-2b), 4.03–3.99 (m, 2H,
ꢁ
ꢁ
0
C for 2 h and at 5 C overnight. The solution was diluted with H-3b, CH
2
Cl), 3.97 (d, J ¼ 1.8 Hz, 1H, CH Cl), 3.95 (d, J ¼ 1.2 Hz,
2
ꢁ
CH
2
Cl
2
(20 mL) at 5 C, quenched with aqueous NaHCO
3
and 1H, 0.6H, H-3b), 3.93 (dt, J ¼ 3.0, 1.8 Hz, 1-H, H-3a), 3.77–3.76
OMe), 2.11 (s, 3H, CH OAc), 2.05 (s, 3H,
OAc); C NMR (150 MHz, CDCl ) d 170.1 (C), 169.6 (C),
H
2
O (10 mL each), and then extracted with (25 mL ꢃ 3). The (m, 3H, 2 ꢃ CH
3
3
1
3
organic fractions were dried over MgSO
4
and concentrated CH
3
3
under reduced pressure. Purication by silica gel ash chro- 168.2 (C), 167.3 (C), 166.3 (C), 136.4 (C), 128.6 (CH ꢃ 2), 128.5
matography [EtOAc–hexanes (1 : 4 to 1 : 1) + 1% Et N] yielded 15 (CH), 128.4 (CH), 128.0 (CH ꢃ 2), 127.8 (CH), 92.8 (CH), 91.9
3
(
971 mg, 68%) as a colourless oil. R ¼ 0.3 (EtOAc–hexane ¼ 1/2); (CH), 73.4 (CH ), 73.1 (CH ), 72.6 (CH), 72.2 (CH), 71.7 (CH),
f
2
2
28
D
[a]
¼ ꢀ0.5 (c 1.0, CH
2
Cl
2
); IR (KBr) n 3570, 3030, 1762, 1737, 68.5 (CH), 68.5 (CH), 67.6 (CH), 66.5 (CH), 65.3 (CH), 52.6 (CH),
ꢀ1
1
+
1
511, 1441 cm ; H NMR (600 MHz, CDCl
3
) d 7.39–7.31 (m, 5H, 40.2 (CH
NaCl 439.0766, found: 439.0783.
Methyl 2-O-acetyl-3-O-benzyl-4-O-(chloroacetyl)-2-O-acetyl-L-
3 3 21
), 40.2 (CH ) ppm. HRMS (M + Na ) calcd for C18H -
Ph), 5.50 (d, J ¼ 1.8 Hz, 1H, H-1), 4.71 (d, J ¼ 11.4 Hz, 1H,
CH Ph), 4.48 (s, 1H, H-4), 4.15–
Ph), 4.64 (d, J ¼ 11.4 Hz, 1H, CH
.08 (m, 2H, H-2, H-5), 3.81 (s, 3H, CO CH ), 3.29 (s, 3H, OCH
O
9
2
2
4
2
3
3
), idopyranuronate trichloroacetimidate (4). Trichloroacetonitrile
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RSC Adv., 2015, 5, 19027–19033 | 19031