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4.2. Tetra-O-acetyl-a-L-glucopyranosyl bromide (5a)
4.8. 1,5-Anhydro-2,3,4,6-tetra-O-benzyl-L-glucitol (8a)
Compound 4a (1.03 g, 2.64 mmol) was dissolved in
AcOH (3.5 mL). Ac2O (0.5 mL) was added followed
by fresh HBr/AcOH 33% (3.5 mL) and stirred for
90 min at rt. Argon was flushed through the solution
for 15 min. The solution was then lyophilized to give
crude material that was used in the next step without
further purification.
Compound 7a (374 mg, 2.28 mmol) was dissolved in
freshly distilled DMF (9.5 mL) and NaH (1.2 g) was
added under Ar. The mixture was cooled to 10 ꢁC
and BnBr (2.0 mL, 17 mmol) was added dropwise.
The mixture was stirred at rt for 16 h. MeOH
(10 mL) was slowly added, followed by H2O
(11 mL). HCl (4 M) was added until the solution be-
comes neutral. The crude product was extracted with
CH2Cl2 and the organic phase was washed with
H2O, dried (MgSO4), and concentrated. The residue
4.3. Tetra-O-acetyl-a-D-glucopyranosyl bromide (5b)
Synthesized as compound 5a.
was chromatographed (SiO2, 3:1 heptane/EtOAc) to
21
give 8a (1.05 g, 87%) as a colorless syrup. ½aꢁ ꢀ9.8
D
4.4. 2,3,4,6-Tetra-O-acetyl-1,5-anhydro-L-glucitol (6a)
(c 1.0 in CDCl3). 1H NMR (CDCl3): d 7.19–7.32
(m, 18H; ArH), 7.07–7.11 (m, 2H; ArH), 4.80, 4.93
(ABq, 1H each, J = 11.0 Hz; OBn), 4.45, 4.78 (ABq,
1H each, J = 10.7 Hz; OBn), 4.59, 4.67 (ABq, 1H
each, J = 11.6 Hz; OBn), 4.46, 4.54 (ABq, 1H each,
J = 12.2 Hz; OBn), 3.99 (dd, 1H, J1 = 11.1 Hz,
J2 = 4.7 Hz; H-1e), 3.48–3.66 (m, 5H; H-2, H-3, H-
6 · 2, H-4), 3.33 (ddd, 1H, J1 = 9.5 Hz, J2 = 4.3 Hz,
J3 = 2.1 Hz ; H-5), 3.12–3.21 (m, 1H; H-1a); 13C
NMR data (CDCl3): d 139.0, 138.38, 138.36, 138.1,
128.7, 128.6, 128.2, 128.15, 128.11, 128.08, 127.93,
127.91, 127.8, 86.6, 79.5, 78.7, 78.0, 75.8, 75.3, 73.8,
73.5, 69.2, 68.4; HRMS calcd for C34H37O5 (M+H):
525.2641, found: 525.2639.
The crude compound 5a was dissolved in dry Et2O
(4.6 mL) under Ar. Bu3SnH (0.780 mL, 2.90 mmol)
was added to the solution followed by a catalytic
amount of AIBN. The solution was stirred in rt for
30 min. KF (0.520 g) dissolved in H2O (2 mL) was add-
ed and the mixture was stirred rapidly for 20 min. The
mixture was filtered through Celite and the filter cake
was washed with Et2O. The H2O phase was extracted
with Et2O. The organic phases were washed with
H2O, concentrated, and recrystallized from Et2O and
pentane to give 6a (0.844 g, 96%) as white crystals;
21
1
mp 70–71 ꢁC; ½aꢁ ꢀ40.0 (c 0.7 in CDCl3); H NMR
D
(CDCl3): d 5.21 (t, 1H, J = 9.5 Hz; H-3), 4.99–5.06
(m, 2H, H-2, H-4), 4.12–4.24 (m, 3H; H-1e, 2· H-6),
3.58–3.63 (m, 1H; H-5), 3.31 (t, 1H, J = 11.0 Hz; H-
1a), 2.10, 2.04, 2.04, 2.02, (s, 3H each; OAc); 13C
NMR data (CDCl3): d 170.9, 170.6, 170.0, 169.7,
76.7, 73.9, 69.2, 68.6, 67.1, 62.4, 21.0, 20.95, 20.92,
20.8; HRMS calcd for C14H21O9 (M+H): 333.1186,
found: 333.1193.
4.9. 1,5-Anhydro-2,3,4,6-tetra-O-benzyl-D-glucitol (8b)
Synthesized as compound 8a (6.90 g, 83%). ½aꢁ21 +10.6 (c
D
21
D
+27 (c 0.5 in CHCl3)].
20
D
0.9 in CHCl3), ½aꢁ +27.1 (c 0.8 in CH2Cl2); [lit.9 ½aꢁ
4.10. 1,5-Anhydro-2,3,4-tri-O-benzyl-L-glucitol (9a)
4.5. 2,3,4,6-Tetra-O-acetyl-1,5-anhydro-D-glucitol (6b)
Compound 8a (1.02 g, 1.95 mmol) was dissolved in
distilled toluene (27 mL). DIBAL (20 mL, 1 M in
CH2Cl2), was added dropwise under Ar. The tempera-
ture was increased to 50 ꢁC and the mixture was stir-
red for 2 h. The solution was poured on ice, HCl
(26 mL, 1 M) was added and the mixture was stirred
rapidly for 10 min. The mixture was diluted with
EtOAc (100 mL) and the H2O phase was extracted
with EtOAc. The combined organic phases were
washed with NaCl (satd aq), dried (MgSO4), and
concentrated. The residue was chromatographed
21
Synthesized as compound 6a (3.30 g, 97%). ½aꢁ +42.3 (c
D
1.0 in CHCl3); [lit.19 [a]D +42.6 (c 1.4 in CHCl3)].
4.6. 1,5-Anhydro-L-glucitol (7a)
Compound 6a (0.813 g, 2.45 mmol) was dissolved in
NaOMe/MeOH (20 mL, 0.05 M) and stirred for
45 min at rt. Amberlite IR-120 H+ was added and stir-
red until the solution turned neutral. The Amberlite
was filtered off and washed with MeOH. The organic
(SiO2, 1:1 heptane/EtOAc) to give 9a (733 mg, 87%)
20
phase was concentrated to give 7a (382 mg, 95%) as a
as a white amorphous solid. ½aꢁ ꢀ17.0 (c 0.6 in
D
21
white amorphous solid; ½aꢁ ꢀ39.0 (c 0.5 in MeOD);
CHCl3) 1H NMR (CDCl3): d 7.28–7.38 (m, 15H;
ArH), 4.88, 5.00 (ABq, 1H each, J = 11.0 Hz; OBn),
4.65, 4.90 (ABq, 1H each, J = 11.0 Hz; OBn), 4.65,
4.74 (ABq, 1H each, J = 11.6 Hz; OBn), 4.01 (dd,
1H, J1 = 11.0 Hz, J2 = 4.9 Hz; H-1e), 3.81–3.87 (m,
1H; H-1e), 3.58–3.70 (m, 3H; H-2, H-3, H-6), 3.50 (t,
1H, J = 9.1 Hz; H-4), 3.27–3.32 (m, 2H; H-5, H-6),
3.24 (t, 1H, J = 10.7 Hz; H-1a), 1.76 (t, 1H, J =
6.45 Hz; OH); 13C NMR data (CDCl3): d 138.9,
138.34, 138.27, 128.7, 128.6, 128.3, 128.12, 128.06,
127.9, 86.4, 79.9, 78.8, 77.8, 75.8, 75.4, 73.6, 68.2,
62.5; HRMS calcd for C27H31O5 (M+H): 435.2171,
found: 435.2182.
D
1H NMR (MeOD): d 3.89 (dd, 1H, J1 = 11.0 Hz,
J2 = 5.4 Hz, H-1), 3.83 (dd, 1H, J1 = 11.8 Hz,
J2 = 2.1 Hz; H-6), 3.60 (dd, 1H, J1 = 11.8 Hz,
J2 = 5.8 Hz, H-6), 3.19–3.49 (m, 5H; H-1, H-2, H-3,
H-4, H-5); 13C NMR data (MeOD): d 82.6, 80.1, 72.0,
71.6, 71.1, 63.2; HRMS calcd for C6H12O5Na
(M+Na): 187.0582, found: 187.0578.
4.7. 1,5-Anhydro-D-glucitol (7b)
21
Synthesized as compound 7a (1.6 g, 98%). ½aꢁ +41.9 (c
D
25
D
0.7 in MeOH); [lit.9 ½aꢁ +42 (c 0.5 in H2O)].