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0.08 mol) were dissolved in acetic acid (100 mL). The mixture was
heated to 55 °C, and then a solution of compound 15b (9.9 g,
0.026 mol) in acetic acid (50 mL) was added. The resulting solution
was stirred under N2 for 6 h at 55 °C. The mixture was then poured
into ice (300 g) and neutralized with saturated aqueous Na2CO3
solution. The mixture was extracted with hexane (2 × 50 mL), then
with EtOAc (3 × 100 mL). The hexane extract was discarded, and
the combined EtOAc phases were washed with saturated aqueous
Na2CO3 and water (100 mL). The organic phase was dried (MgSO4),
filtered, and concentrated in vacuo. The residue was dissolved in
diethyl ether (50 mL) and crystallized from hexane to give 16 (6.4 g,
62 %) as white crystals. Rf = 0.52 (EtOAc/petroleum ether, 1:1). M.p.
(BnO-3: C-2′, C-3′, C-4′, C-5′, C-6′), 127.45, 127.41, 126.4 (BnO-2:
C-2′, C-3′, C-4′, C-5′, C-6′), 97.7 (C-1), 81.4 (C-3), 80.0 (C-2), 72.5 (BnO-
2: CH2′), 72.0 (BnO-3: CH2′), 70.4 (C-5), 62.9 (C-6), 54.8 (CH3), 54.6 (C-
4) ppm.
Data for compound 14: Rf = 0.22 (EtOAc/methanol, 9:1). 1H NMR
3
(CDCl3): δ = 7.28–7.16 (m, BnO-2 Ar-H, BnO-3 Ar-H), 4.95 (d, JH,H
=
3
11.4 Hz, 1 H, BnO-3: CH2A), 4.71 (overlapped d, JH,H = 12.1 Hz, 1 H,
BnO-2: CH2A), 4.64 (overlapped m, 1 H, BnO-2: CH2B), 4.57 (over-
3
lapped d, JH,H = 11.4 Hz, 1 H, BnO-3: CH2B), 4.57 (overlapped, 1 H,
3
1-H), 3.73 (overlapped t, JH,H = 5.6 Hz, 1 H, 5-H), 3.72 (overlapped
3
3
t, JH,H = 5.2 Hz, 1 H, 6-HA), 3.72 (overlapped t, JH,H = 9.8 Hz, 1 H,
3
3
3-H), 3.69 (overlapped t, JH,H = 5.2 Hz, 1 H, 6-HB), 3.6 (dd, JH,H
=
1
91 °C. [α]2D2 = +101.3 (c = 1, chloroform). H NMR (CDCl3): δ = 9.13
6.4, 3.7 Hz, 1 H, 2-H), 3.27 (s, 3 H, CH3), 3.21 (dd, 3JH,H = 3.8 Hz, 1 H,
4-H), 2.29 (br., 1 H, 6-OH) ppm. 13C NMR (CDCl3): δ = 137.9, 137.5
(BnO-2: C-1′ and BnO-3: C-1′), 128.1, 128.06, 127.2 (BnO-3: C-2′, C-
3′, C-4′, C-5′, C-6′), 127.6, 127.5, 126.9 (BnO-2: C-2′, C-3′, C-4′, C-5′,
C-6′), 98.11 (C-1), 77.4 (C-5), 75.1 (BnO-3: CH2′), 75.0 (C-2), 72.8 (BnO-
2: CH2′), 68.1 (C-3), 62.4 (C-6), 54.7 (CH3), 51.1 (C-4) ppm.
3
(s, 1 H, OH-oxime), 7.24–7.15 (m, BnO Ar-H), 4.96 (dd, JH,H = 5.3,
3
3
1.8 Hz, 1 H, 5-H), 4.76 (d, JH,H = 3.7 Hz, 1 H, 1-H), 4.53 (d, JH,H
=
3
11.6 Hz, 1 H, BnO-3: CH2A), 4.51 (d, JH,H = 12.1 Hz, 1 H, BnO-2:
CH2A), 4.45 (d, JH,H = 12.1 Hz, 1 H, BnO-2: CH2B), 4.28 (d, JH,H
3
3
=
3
11.6 Hz, 1 H, BnO-3: CH2B), 4.06 (d, JH,H = 3.4 Hz, 1 H, 3-H), 3.86
(dt, 3JH,H = 11.5, 5.0 Hz, 1 H, 6-HA), 3.78–3.74 (overlapped m, 1 H, 6-
3
HB), 3.77 (overlapped t, JH,H = 3.6 Hz, 1 H, 2-H), 3.36 (s, 3 H, CH3),
Methyl N-9-Fluorenylmethoxycarbonyl-2,3-di-O-benzyl-4-
2.72 (very br. t, 1 H, 6-OH) ppm. 13C NMR (CDCl3): δ = 153.0 (C-4),
137.6 (BnO-3: C-1′), 137.1 (BnO-2: C-1′), 128.6, 128.5, 128.4 (BnO-3:
C-2′, C-3′, C-4′, C-5′, C-6′), 128.2, 128.1, 128.0 (BnO-2: C-2′, C-3′,
C-4′, C-5′, C-6′), 97.2 (C-1), 79.0 (C-2), 76.6 (C-3), 72.1 (BnO-2: CH2′),
70.6 (BnO-3: CH2′), 68.5 (C-5), 62.1 (C-6), 56.6 (CH3) ppm. HRMS:
calcd. for C21H26NO6 [M + H]+ 388.1760; found 388.1761.
amino-4-deoxy-α-
Fluorenylmethoxycarbonyl-2,3-di-O-benzyl-4-amino-4-deoxy-
α- -galactopyranoside (21): The mixture of compounds 14 and
D-glucopyranoside (20) and Methyl N-9-
D
17 (2.23 g, 6 mmol) was dissolved in a mixture of methanol and
water (2:1; 48 mL), and the pH was adjusted to 9 with saturated
aqueous NaHCO3. Then, a solution of Fmoc-OSu (2.21 g, 6.53 mmol)
in THF (15 mL) was added, and the mixture was stirred for 24 h.
After this time, the THF was evaporated, and the residue was ex-
tracted with hexane (2 × 50 mL), then with EtOAc (3 × 50 mL). The
hexane extract was discarded. The combined EtOAc phases were
washed with brine (100 mL), dried (MgSO4), filtered and concen-
trated in vacuo. The residue was treated with ether to give com-
pound 20 (1.7 g, 96 %) as a white solid. Rf = 0.15 (ether/petroleum
ether, 4:1). [α]2D2 = +28.3 (c = 1, chloroform). 1H NMR (CDCl3): δ =
Methyl 2,3-Di-O-benzyl-4-deoxy-4-hydroxylamino-α-
pyranoside (18) and Methyl 2,3-Di-O-benzyl-4-deoxy-4-hydrox-
ylamino-α- -galactopyranoside (19): NaBH4 (2.93 g, 0.077 mol)
D-gluco-
D
was added in small portions to glacial acetic acid (50 mL) at 15–
20 °C. The mixture was stirred for 30 min, then 16 (5 g, 0.013 mol)
was added in one portion. The mixture was stirred at room temper-
ature for 2 h. Water (10 mL) was then added, and the mixture was
neutralized with saturated aqueous Na2CO3. The mixture was ex-
tracted with dichloromethane (2 × 100 mL), and the combined or-
ganic phases were washed with saturated aqueous Na2CO3
(100 mL), dried (MgSO4), and filtered. The mixture was concentrated
in vacuo to give a mixture of 18 and 19 (4.9 g, 98 %) as a colourless
oil. Rf = 0.41 and 0.46 (EtOAc/petroleum ether, 1:1). The mixture of
18 and 19 was subsequently converted into the corresponding
amine derivatives without prior separation.
3
7.68 (dd, JH,H = 2.4, 7.2 Hz, 2 H, Fmoc-6-H, Fmoc-6′-H), 7.46 (dd,
3JH,H = 7.0, 3.0 Hz, 2 H, Fmoc-3-H, Fmoc-3′-H), 7.34–7.15 (m, BnO
3
Ar-H, Fmoc-4-H, Fmoc-5-H, Fmoc-4′-H, Fmoc-5′-H), 4.81 (d, JH,H
=
3
11.7 Hz, 1 H, BnO-3: CH2A), 4.70 (d, JH,H = 11.2 Hz, 1 H, BnO-2:
CH2A), 4.58 (overlapped, 2 H, BnO-2: CH2B, BnO-3: CH2B), 4.53 (d,
3
3JH,H = 3.3 Hz, 1 H, 1-H), 4.48 (dd, JH,H = 10.7, 4.2 Hz, 1 H, Fmoc-
CH2A), 4.36 (dd, 3JH,H = 10.7, 4.2 Hz, 1 H, Fmoc-CH2B), 4.25 (d, 3JH,H
6.9 Hz, 1 H, NH), 4.08 (t, JH,H = 6.1 Hz, 1 H, Fmoc-1-H), 3.58 (over-
=
3
3
3
Methyl 2,3-Di-O-benzyl-4-amino-4-deoxy-α-
(17) and Methyl 2,3-Di-O-benzyl-4-amino-4-deoxy-α-
D
-glucopyranoside
-galacto-
lapped dd, JH,H = 9.8, 3.5 Hz, 1 H, 4-H), 3.57 (overlapped t, JH,H =
3
D
9.5 Hz, 1 H, 3-H), 3.52 (overlapped dd, JH,H = 8.8, 3.2 Hz, 1 H, 2-H),
3.46 (dd, 3JH,H = 12.7, 7.2 Hz, 1 H, 6-HA), 3.40 (dd, 3JH,H = 12.7, 7.2 Hz,
1 H, 6-HB), 3.25 (overlapped s, 3 H, CH3), 3.25 (overlapped m, 1 H,
5-H) ppm. 13C NMR (CDCl3): δ = 157.1 (Fmoc-C=O), 143.9, 143.3
(Fmoc-C-2 and Fmoc-C-2′), 140.9 (Fmoc-C-7 and Fmoc-C-7′), 137.6
(BnO-3: C-1′′), 137.3 (BnO-2: C-1′), 128.1, 128.0 (Fmoc-C-4 and Fmoc-
pyranoside (14) by Nonselective Oxime Reduction: The mixture
of 18 and 19 (4.8 g, 0.012 mol) was dissolved in methanol (620 mL),
and was reduced in an H-cube reactor. The flow velocity was set
with an HPLC pump to 0.3 mL/min; the hydrogen pressure was set
to 50 bar; the temperature to 80 °C; a cartridge containing RaNi
was used. The resulting solution was concentrated in vacuo to give C-4′ and Fmoc-C-5 and Fmoc-C-5′), 127.9, 127.8, 127.6, 127.3 (BnO-
a mixture of 14 and 17 (4.35 g, 97 %) as a colourless oil. The mixture
of 14 and 17 was subsequently converted into the corresponding
Fmoc derivatives without prior separation.
3: C-2′′, C-3′′, C-4′′, C-5′′, and BnO-2: C-2′, C-3′, C-4′, C-5′), 127.6
(BnO-3: C-6′′), 127.5 (BnO-2: C-6′), 124.4 (Fmoc-C-3 and Fmoc-C-3′),
119.6 (Fmoc-C-6 and Fmoc-C-6′), 97.8 (C-1), 79.6 (C-2), 75.9 (C-3),
74.0 (BnO-3: CH2′′), 72.8 (BnO-2: CH2′), 70.9 (C-5), 66.2 (Fmoc-CH2),
54.8 (CH3), 51.4 (C-4), 46.8 (Fmoc-C-1) ppm. HRMS: calcd. for
C36H38NO7 [M + H]+ 596.2648; found 596.2631.
Data for compound 17: Rf = 0.31 (EtOAc/methanol, 9:1). 1H NMR
3
(CDCl3): δ = 7.28–7.16 (m, BnO Ar-H), 4.65 (overlapped d, JH,H
=
3
11.5 Hz, 1 H, BnO-3: CH2A), 4.57 (overlapped d, JH,H = 11.5 Hz, 1 H,
BnO-3: CH2B), 4.57 (overlapped m, 1 H, BnO-2: CH2A), 4.55 (over- The mother liquor was concentrated and treated with hexane to
3
lapped m, 1 H, BnO-2: CH2B), 4.52 (d, JH,H = 3.6 Hz, 1 H, 1-H), 3.63
give compound 21 (1.3 g, 75 %) as a white viscous liquid. Rf = 0.23
3
3
(overlapped dd, JH,H = 6.3 Hz, 2 H, 6-HA and 6-HB), 3.47 (t, JH,H
=
(ether/petroleum ether, 4:1). [α]2D2 = +44 (c = 0.5, chloroform). 1H
9.5 Hz, 1 H, 3-H), 3.41 (dd, JH,H = 9.7, 3.3 Hz, 1 H, 2-H), 3.36 (over- NMR (CDCl3): δ = 7.69 (d, 3JH,H = 7.6 Hz, 2 H, Fmoc-6-H, Fmoc-6′-H),
3
lapped dd, 3JH,H = 5.1 Hz, 1 H, 5-H), 3.27 (s, 3 H, CH3), 2.60 (t, 3JH,H
=
7.50 (t, JH,H = 6.4 Hz, 2 H, Fmoc-4-H, Fmoc-4′-H), 7.33–7.17 (m, 14
H, BnO-2 Ar-H, BnO-3 Ar-H, Fmoc-3-H, Fmoc-5-H, Fmoc-3′-H, Fmoc-
3
9.5 Hz, 1 H, 4-H), 2.29 (very br., 1 H, 6-OH) ppm. 13C NMR (CDCl3):
3
3
δ = 138.1, 137.8 (BnO-2: C-1′ and BnO-3: C-1′), 128.03, 127.9, 127.3 5′-H), 4.92 (d, JH,H = 8.5 Hz, 1 H, NH), 4.77 (d, JH,H = 12.8 Hz, 1 H,
Eur. J. Org. Chem. 2018, 355–361
359 © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim