European Journal of Organic Chemistry
10.1002/ejoc.201800245
FULL PAPER
3
(
2
2
C-3 β), 72.6 (C-3 α), 39.4, 39.2 (C-7 α, β), 32.1, 29.8, 29.8, 29.7, 29.7,
α, β), 1.32-1.19 (m, 36 H, CH
2
-9 to CH
-18) ppm. C NMR (CDCl
2
-17, α, β), 0.88 (t, J = 6.8 Hz, 6 H,
13
9.6, 29.5, 29.4, 27.0, 27.0, 22.8 (C-8 to C-17, α, β), 21.2, 21.1, 20.8,
0.8, 20.7, 20.6 (CH , Ac, α, β), 14.3 (C-18 α, β) ppm. HRMS: calcd for
[M + H] 578.3324, found 578.3302.
CH
3
3
, 100MHz): δ = 170.0, 169.5, 169.4, 169.3,
3
169.0, 168.8 (CO, amide, CO, Ac, α, β), 136.7, 136.6 (Cq, Ph, α, β),
128.9, 128.8, 128.7, 128.5, 128.5 (CH, Ph, α, β), 93.4 (C-1 β), 89.4 (C-1
α), 81.6 (C-4 β), 80.0 (C-2 β), 78.5 (C-5 α), 78.0 (C-4 α), 77.6 (C-5 β),
+
31 9
C H47NO
7
3
2
6.0 (C-2 α), 74.5, 73.8 (CH
9.3 (C-7, α, β), 32.0, 29.8, 29.8, 29.8, 29.7, 29.7, 29.7, 29.6, 29.6, 29.5,
9.4, 27.0, 27.0, 22.8 (C-8 to C-17, α, β), 20.8, 20.7, 20.7, 20.6 (CH
2
Ph, α, β), 73.5 (C-3 α), 73.3 (C-3 β), 39.4,
N-Dodecyl
1,2-di-O-acetyl-3,5-di-O-benzyl-α,β-D-
glucofuranuronamide (16-α,β): According to the general procedure, the
hydrolysis of N-dodecyl 3,5-di-O-benzyl-1,2-O-isopropylidene-α-D-
glucofuranuronamide (12, 846 mg, 1.45 mmol) in aq. TFA (60%, 8 mL),
which was completed within 1.5 h, was followed by acetylation using a
mixture of pyridine (6.3 mL) and acetic anhydride (4.2 mL) during 1.5 h.
After purification by column chromatography (EtOAc/hexane, 1:2), 16
3
,
+
44 4 7
OAc, α, β), 14.3 (C-18, α, β) ppm. HRMS: calcd for C29H N O [M + H]
561.3283, found 561.3270.
N-Dodecyl
2-O-acetyl-1-azido-3,5-di-O-benzyl-1-deoxy-α-D-
(
760 g, 84%, anomeric mixture α/β, ratio, 1:0.8) was obtained as a pale
glucofuranuronamide (17-α) and N-dodecyl 2-O-acetyl-1-azido-3,5-
di-O-benzyl-1-deoxy-β-D-glucofuranuronamide (17-β): According to
the general procedure, the reaction of N-dodecyl 1,2-di-O-acetyl-3,5-di-
O-benzyl-α,β-D-glucofuranuronamide (16-α,β, 418 mg, 0.67 mmol) with
1
3
yellow oil. H NMR (CDCl , 400 MHz): δ = 7.48-7.27 (m, 18 H, Ph, α, β),
3
3
6
.60 (t, J = 5.7 Hz, 1 H, NH α), 6.52 (t, J = 5.3 Hz, 0.8 H, NH β), 6.40 (d,
3
3
J
1,2α = 4.6 Hz, 1 H, 1-H α), 6.12 (br. d, 0.8 H, 1-H β), 5.50-5.39 (m, J2,3 α
7.7, J1,2 β = 1.3 Hz, J2,3 β = 2.8 Hz, 1.8 H, 2-H α, 2-H β), 4.97 (dd, J3,4 α
7.7 Hz, J4,5 α = 3.4 Hz, 1 H, 4-H α), 4.81 (d, part A of AB system, Ja,b α
11.5 Hz, 1 H, a-H α from CH
3
3
3
=
=
=
8
3
TMSN (95%, 0.84 mL, 6.01 mmol) in the presence of TMSOTf (0.97 mL,
3
2
5.34 mmol) under MW irradiation during 70 min and further purification by
column chromatography (EtOAc/hexane, 1:3) gave 17-α (116.4 mg,
29%) and 17-β (119.4 mg, 29%) as colourless oils.
3
3
2
Ph), 4.73-4.43 (m, J2,3 α = J3,4 α = 7.7 Hz,
Ph β, 4-H β, 3-H α), 4.31 (d, J4,5 β = 6.2
3
H, b-H α, Bn, CH Ph α, 2 × CH
2
2
3
Hz, 0.8 H, 5-H β), 4.23-4.18 (m,
3
2
α, β), 1.34-1.08 (m, 36 H, CH
H, CH
1
1
1
9
7
J
4,5 α = 3.4 Hz, 1.8 H, 3-H β, 5-H α),
.30-3.12 (m, 1.8 H, 7a-H α, 7a-H β), 3.00-2.90 (m, 0.8 H, 7b-H β), 2.74-
.63 (m, 0.8 H, 7b-H β), 2.05, 2.04, 1.99, 1.98 (4 s, 10.8 H, 2 × CH , Ac,
-17, α, β), 0.88 (t, J = 6.7 Hz, 5.4
-18, α, β) ppm. C NMR (CDCl , 100MHz): δ = 169.9, 169.8,
69.8, 169.7, 169.7 (CO, Ac, α, β), 169.3 (CO, amide, α, β) 137.7, 137.6,
20
D
1
Data for 17-α:
= + 36 (c = 0.5, in CH
2
Cl
2
). H NMR (CDCl
3
, 400
3
3
MHz): δ = 7.40-7.22 (m, 10 H, Ph), 6.45 (t, J = 5.6 Hz, 1 H, NH), 5.60 (d,
1,2 = 5.1 Hz, 1 H, 1-H), 5.25 (dd, J2,3 = 6.5 Hz, 1 H, H-2), 4.84 (dd, J3,4
7.1 Hz, J4,5 = 4.3 Hz, 1 H, 4-H), 4.70 (d, part A of AB system, J = 11.4
3
-8 to CH
2
3
3
3
2
J
13
3
2
3
3
=
2
Hz, 1 H, a-H from 5-CH
H, b-H from 5-CH
2
Ph), 4.59 (d, part B of AB system, J = 11.4 Hz,
Ph), 4.53 (br.s, 2 H, 3-CH Ph), 4.34 (t, 1 H, 3-H),
.21 (d, J4,5 = 4.3 Hz, 1 H, 5-H), 3.27-3.16 (m, 1 H, 7a-H), 2.85-2.75 (m,
H, 7b-H), 2.05 (s, CH , OAc), 1.34-1.11 (m, 20 H, CH -8 to CH -17),
, 100 MHz): δ =
37.4 136.9 (4 × Cq, Ph, α, β), 128.8, 128.6, 128.5, 128.4, 128.4, 128.3,
28.1, 127.9, 127.8, 127.8, 127.5, 127.5 (CH, Ph, α, β), 99.5 (C-1 β),
2.8 (C-1 α), 82.2 (C-4 β), 80.4 (C-3 β), 79.9 (C-5 α), 79.1 (C-3 α), 78.9,
8.9 (C-2 β, C-5 β), 78.4 (C-4 α), 75.9 (C-2 α), 75.6, 74.2, 73.3, 72.3
1
4
1
0
1
1
3
3
2
2
2
3
3
2
2
3
13
3 3
.88 (t, 3 H, CH -18, J = 6.8 Hz) ppm. C NMR (CDCl
(
2
CH
2
, Bn, α, β), 39.1, 38.9 (C-7 α, β), 32.0, 29.7, 29.7, 29.6, 29.6, 29.4,
9.3, 29.2, 26.9, 26.9, 22.7 (C-8 to C-17, α, β), 21.1, 20.8, 20.5 (CH , Ac,
[M + H]
70.1 (CO, Ac), 169.2 (CO, amide), 137.5, 136.9 (2 × Cq, 2 × Ph), 128.7,
28.4, 128.4, 127.9, 127.6 (CH, 2 × Ph), 89.0 (C-1), 79.7 (C-5), 79.5 (C-
Ph-5), 73.2 (CH Ph-3), 38.9 (C-7),
2 2
1.9, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 29.3, 26.9, 22.7 (C-8 to C-17),
3
+
α, β), 14.2 (C-18 α, β) ppm. HRMS: calcd for C36
6
H51NO
8
), 78.4 (C-4), 76.8 (C-2), 75.1 (CH
26.3687, found 626.3682.
+
3 48 4 6
0.5 (CH ), 14.2 (C-18) ppm. HRMS: calcd for C34H N O [M + H]
General procedure for the synthesis of N-dodecyl 1-azido-α,β-D-
glucofuranuronamides: To solution of N-dodecyl
609.3647, found 609.3639.
a
20
D
1
glucofuranuronamide (0.19 mmol) in acetonitrile (5 mL), trimethylsilyl
azide (9 equiv.) and TMSOTf (8 equiv.) were sequentially added. The
solution was stirred at 65ºC under microwave irradion (150 W, P max =
Data for 17-β:
2 2 3
= ‒ 29 (c = 0.34, in CH Cl ). H NMR (CDCl , 400
3
MHz): δ = 7.40-7.20 (m, 10 H, Ph), 6.20 (t, J = 5.7 Hz, 1 H, NH), 5.22 (br.
3
3
2
t, J = 1.6 Hz, 1 H, 2-H), 5.18 (d,
1.4 Hz, 1 H, a-H from 3-CH
J
1,2 = 1.1 Hz, 1 H, 1-H), 4.75 (d, J =
Ph), 4.59-4.46 (m, 4 H, b-H from 3-CH Ph,
Ph, 4-H), 4.25 (d, J4,5 = 7.7 Hz, 1 H, 5-H), 4.11 (dd, J2,3 = 1.6 Hz,
3,4 = 4.5 Hz, 1 H, 3-H), 3.35-3.24 (m, 1 H, 7a-H), 3.13-3.03 (m, 1 H, 7b-
, OAc), 1.43-1.33 (m, 2 H, CH -8), 1.32-1.19 (m, 18 H,
2
50 Psi) for 20-70 min. The solution was then diluted with CH
neutralized witg sat. aq. NaHCO soln. The aqueous phase was
extracted with dichloromethane (3×) and the combined organic phases
were dried with anhydrous MgSO . After filtration and evaporation , the
2 2
Cl and
1
2
2
3
3
3
5
J
-CH
2
3
4
H), 2.05 (s, CH
CH -9 to CH -17), 0.88 (t, J = 6.8 Hz, 3 H, CH
CDCl , 100MHz): δ = 169.8 (CO, amide), 169.6 (CO, Ac), 137.2, 137.2
2 × Cq, 2 × Ph), 128.5, 128.5, 128.2, 128.1, 127.9, 127.7 (CH, 2 × Ph),
Ph-5),
Ph-3), 39.3 (C-7), 32.0, 29.7, 29.7, 29.6, 29.6, 29.5, 29.4, 29.3,
26.9, 22.7 (C-8 to C-17), 20.8 (CH ), 14.2 (C-18) ppm. HRMS: calcd for
[M + H] 609.3647, found 609.3643.
3
2
crude was subjected to purification by column chromatography on silica
gel.
3
13
2
2
3
-18) ppm. C NMR
(
(
3
N-Dodecyl
glucofuranuronamide (14-α,β): According to the general procedure, the
reaction of N-dodecyl 1,2-di-O-acetyl-5-O-benzyl-α,β-D-
glucofuranuronamide (13-α,β, 112 mg, 0.19 mmol) with TMSN (95%,
.25 mL, 1.75 mmol) in the presence of TMSOTf (0.28 mL, 1.55 mmol)
2,3-di-O-acetyl-1-azido-5-O-benzyl-1-deoxy-α,β-D-
93.3 (C-1), 82.5 (C-4), 80.0 (C-3), 78.9 (C-2), 77.6 (C-5), 73.5 (CH
72.3 (CH
2
2
3
+
3
C H N O
34 48 4 6
0
under MW irradiation during 20 min and further purification by column
General procedure for the CuI/Amberlyste A21-catalysed
chromatography (EtOAc/hexane, 1:2) gave 14-α,β (94 mg, 87%,
cycloaddition of N-dodecyl 1-azido glucofurauronamide derivatives
1
anomeric mixture α/β, ratio, 1:1) as colourless oil. H NMR (CDCl
MHz): δ = 7.43-7.28 (m, 10 H, Ph), 6.49, 6.35 (2 t, J = 5.7 Hz, 2 H, NH, α,
3
, 400
with phenylacetylene: To
glucofuranuronamide derivative (0.11 mmol) in CH
phenylacetylene (0.65 mL) and Amberlyste A21/CuI (0.5 mmol.g , 0.25
equiv. CuI) were added. The mixture was stirred at room temp. for 16-72
h. The catalyst was filtered off, the solvent was evaporated and the
residue was purified by column chromatography.
a
solution of N-dodecyl 1-azido
Cl (2.8 mL),
3
2
2
3
3
3
−
1
β), 5.65 (d, J1,2 α = 5.1 Hz, 1 H, 1-H α,), 5.57 (t, J2,3 α ~ J3,4 α ~ 5.9 Hz, 1
3
3
H, 3-H α,), 5.37 (dd, J2,3 β = 1.6 Hz, J3,4 β = 4.1 Hz, 1 H, 3-H β,), 5.24 (t,
H, 2-H α), 5.14 (d, J1,2 β = 1.0 Hz, 1 H, 1-H β), 5.04 (br. t, 1 H, 2-H β),
3
1
4
3
3
2
.74 (dd, J3,4 α = 5.9 Hz,
J
4,5 α = 4.9 Hz, 1 H, 4-H α,), 4.66 (d, J = 11.5
Ph, CH Ph,
-H β), 4.20 (d, J4,5 α = 6.5 Hz, 1 H, 5-H β), 4.14 (d, J4,5 α = 4.9 Hz, 1 H,
-H α), 3.42-3.29 (m, 2 H, 7a-H, α, β), 3.25-3.04 (m, 4 H, 7b-H, α, β),
.13, 2.10, 1.94, 1.92 (4 s, 4 × CH , OAc, 12 H), 1.55-1.39 (m, 4 H, CH -8,
Hz, 1 H, a-H from CH
2
Ph), 4.62-4.54 (m, 4 H, b-H from CH
2
2
3
3
4
5
2
N-Dodecyl 2,3-di-O-acetyl-5-O-benzyl-1-deoxy-1-(4-phenyltriazol-1-
yl)-α,β-D-glucofuranuronamide (15-α,β): According to the general
procedure, the reaction of N-dodecyl 2,3-di-O-acetyl-1-azido-5-O-benzyl-
3
2
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